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Gerard Conrad Blobe

Professor of Medicine
Medicine, Medical Oncology
Duke Box 91004, Durham, NC 27708-1004
B354 Levine Science Research Center, 450 Research Drive, Durham, NC 27708

Selected Publications


NRP1 interacts with endoglin and VEGFR2 to modulate VEGF signaling and endothelial cell sprouting.

Journal Article Commun Biol · January 19, 2024 Endothelial cells express neuropilin 1 (NRP1), endoglin (ENG) and vascular endothelial growth factor receptor 2 (VEGFR2), which regulate VEGF-A-mediated vascular development and angiogenesis. However, the link between complex formation among these receptor ... Full text Link to item Cite

Assessing the utility of molecular diagnostic classification for cancers of unknown primary.

Journal Article Cancer Med · October 2023 BACKGROUND: Roughly 5% of metastatic cancers present with uncertain origin, for which molecular classification could influence subsequent management; however, prior studies of molecular diagnostic classifiers have reported mixed results with regard to clin ... Full text Link to item Cite

TGF-β superfamily co-receptors in cancer.

Journal Article Dev Dyn · January 2022 Transforming growth factor-β (TGF-β) superfamily signaling via their cognate receptors is frequently modified by TGF-β superfamily co-receptors. Signaling through SMAD-mediated pathways may be enhanced or depressed depending on the specific co-receptor and ... Full text Link to item Cite

The role of the extracellular matrix protein TGFBI in cancer.

Journal Article Cell Signal · August 2021 The secreted extracellular protein, transforming growth factor beta induced (TGFBI or βIGH3), has roles in regulating numerous biological functions, including cell adhesion and bone formation, both during embryonic development and during the pathogenesis o ... Full text Link to item Cite

Cabozantinib and Panitumumab for RAS Wild-Type Metastatic Colorectal Cancer.

Journal Article Oncologist · June 2021 LESSONS LEARNED: Antitumor activity was observed in the study population. Dose modifications of cabozantinib improve long-term tolerability. Biomarkers are needed to identify patient populations most likely to benefit. Further study of cabozantinib with or ... Full text Link to item Cite

ALK1 regulates the internalization of endoglin and the type III TGF-β receptor.

Journal Article Mol Biol Cell · April 1, 2021 Complex formation and endocytosis of transforming growth factor-β (TGF-β) receptors play important roles in signaling. However, their interdependence remained unexplored. Here, we demonstrate that ALK1, a TGF-β type I receptor prevalent in endothelial cell ... Full text Link to item Cite

KEYlargo: A phase II study of first-line pembrolizumab (P), capecitabine (C), and oxaliplatin (O) in HER2-negative gastroesophageal (GE) adenocarcinoma.

Conference Journal of Clinical Oncology · January 20, 2021 228 Background: Gastric and esophageal adenocarcinomas are a leading cause of cancer death worldwide. Many of these patients (pts) present with locally advanced unresectable or metastatic disease and are treated with combination ... Full text Cite

A phase Ib study of the combination regorafenib with PF-03446962 in patients with refractory metastatic colorectal cancer (REGAL-1 trial).

Journal Article Cancer Chemother Pharmacol · October 2019 PURPOSE: This study aimed to evaluate the maximum tolerated dose (MTD) and recommended phase II dose (RPTD), as well as the safety and tolerability of PF-03446962, a monoclonal antibody targeting activin receptor like kinase 1 (ALK-1), in combination with ... Full text Link to item Cite

Increased type III TGF-β receptor shedding decreases tumorigenesis through induction of epithelial-to-mesenchymal transition.

Journal Article Oncogene · May 2019 The type III TGF-β receptor (TβRIII) is a TGF-β co-receptor that presents ligand to the type II TGF-β receptor to initiate signaling. TβRIII also undergoes ectodomain shedding to release a soluble form (sTβRIII) that can bind ligand, sequestering it away f ... Full text Link to item Cite

Stromal Fibroblasts Mediate Anti-PD-1 Resistance via MMP-9 and Dictate TGFβ Inhibitor Sequencing in Melanoma.

Journal Article Cancer Immunol Res · December 2018 Although anti-PD-1 therapy has improved clinical outcomes for select patients with advanced cancer, many patients exhibit either primary or adaptive resistance to checkpoint inhibitor immunotherapy. The role of the tumor stroma in the development of these ... Full text Open Access Link to item Cite

Endoglin interacts with VEGFR2 to promote angiogenesis.

Journal Article FASEB J · June 2018 Endoglin, a TGF-β coreceptor predominantly expressed in endothelial cells, plays an important role in vascular development and tumor-associated angiogenesis. However, the mechanism by which endoglin regulates angiogenesis, especially during tip cell format ... Full text Link to item Cite

Endoglin Mediates Vascular Maturation by Promoting Vascular Smooth Muscle Cell Migration and Spreading.

Journal Article Arterioscler Thromb Vasc Biol · June 2017 OBJECTIVE: Endoglin, a transforming growth factor-β superfamily coreceptor, is predominantly expressed in endothelial cells and has essential roles in vascular development. However, whether endoglin is also expressed in vascular smooth muscle cells (VSMCs) ... Full text Link to item Cite

Heparin-binding epidermal growth factor-like growth factor promotes neuroblastoma differentiation.

Journal Article FASEB J · May 2017 High-risk neuroblastoma is characterized by undifferentiated neuroblasts and low schwannian stroma content. The tumor stroma contributes to the suppression of tumor growth by releasing soluble factors that promote neuroblast differentiation. Here we identi ... Full text Link to item Cite

Phase I study of pazopanib plus TH-302 in advanced solid tumors.

Journal Article Cancer Chemother Pharmacol · March 2017 PURPOSE: To define the maximum tolerated dose (MTD), recommended phase II dose (RPTD), and assess safety and tolerability for the combination of pazopanib plus TH-302, an investigational hypoxia-activated prodrug (HAP), in adult patients with advanced soli ... Full text Link to item Cite

TGF-β-induced stromal CYR61 promotes resistance to gemcitabine in pancreatic ductal adenocarcinoma through downregulation of the nucleoside transporters hENT1 and hCNT3.

Journal Article Carcinogenesis · November 1, 2016 Pancreatic ductal adenocarcinoma (PDAC) is a lethal cancer in part due to inherent resistance to chemotherapy, including the first-line drug gemcitabine. Although low expression of the nucleoside transporters hENT1 and hCNT3 that mediate cellular uptake of ... Full text Link to item Cite

NRP1 interacts with endoglin and VEGFR2 to modulate VEGF signaling and endothelial cell sprouting.

Journal Article Commun Biol · January 19, 2024 Endothelial cells express neuropilin 1 (NRP1), endoglin (ENG) and vascular endothelial growth factor receptor 2 (VEGFR2), which regulate VEGF-A-mediated vascular development and angiogenesis. However, the link between complex formation among these receptor ... Full text Link to item Cite

Assessing the utility of molecular diagnostic classification for cancers of unknown primary.

Journal Article Cancer Med · October 2023 BACKGROUND: Roughly 5% of metastatic cancers present with uncertain origin, for which molecular classification could influence subsequent management; however, prior studies of molecular diagnostic classifiers have reported mixed results with regard to clin ... Full text Link to item Cite

TGF-β superfamily co-receptors in cancer.

Journal Article Dev Dyn · January 2022 Transforming growth factor-β (TGF-β) superfamily signaling via their cognate receptors is frequently modified by TGF-β superfamily co-receptors. Signaling through SMAD-mediated pathways may be enhanced or depressed depending on the specific co-receptor and ... Full text Link to item Cite

The role of the extracellular matrix protein TGFBI in cancer.

Journal Article Cell Signal · August 2021 The secreted extracellular protein, transforming growth factor beta induced (TGFBI or βIGH3), has roles in regulating numerous biological functions, including cell adhesion and bone formation, both during embryonic development and during the pathogenesis o ... Full text Link to item Cite

Cabozantinib and Panitumumab for RAS Wild-Type Metastatic Colorectal Cancer.

Journal Article Oncologist · June 2021 LESSONS LEARNED: Antitumor activity was observed in the study population. Dose modifications of cabozantinib improve long-term tolerability. Biomarkers are needed to identify patient populations most likely to benefit. Further study of cabozantinib with or ... Full text Link to item Cite

ALK1 regulates the internalization of endoglin and the type III TGF-β receptor.

Journal Article Mol Biol Cell · April 1, 2021 Complex formation and endocytosis of transforming growth factor-β (TGF-β) receptors play important roles in signaling. However, their interdependence remained unexplored. Here, we demonstrate that ALK1, a TGF-β type I receptor prevalent in endothelial cell ... Full text Link to item Cite

KEYlargo: A phase II study of first-line pembrolizumab (P), capecitabine (C), and oxaliplatin (O) in HER2-negative gastroesophageal (GE) adenocarcinoma.

Conference Journal of Clinical Oncology · January 20, 2021 228 Background: Gastric and esophageal adenocarcinomas are a leading cause of cancer death worldwide. Many of these patients (pts) present with locally advanced unresectable or metastatic disease and are treated with combination ... Full text Cite

A phase Ib study of the combination regorafenib with PF-03446962 in patients with refractory metastatic colorectal cancer (REGAL-1 trial).

Journal Article Cancer Chemother Pharmacol · October 2019 PURPOSE: This study aimed to evaluate the maximum tolerated dose (MTD) and recommended phase II dose (RPTD), as well as the safety and tolerability of PF-03446962, a monoclonal antibody targeting activin receptor like kinase 1 (ALK-1), in combination with ... Full text Link to item Cite

Increased type III TGF-β receptor shedding decreases tumorigenesis through induction of epithelial-to-mesenchymal transition.

Journal Article Oncogene · May 2019 The type III TGF-β receptor (TβRIII) is a TGF-β co-receptor that presents ligand to the type II TGF-β receptor to initiate signaling. TβRIII also undergoes ectodomain shedding to release a soluble form (sTβRIII) that can bind ligand, sequestering it away f ... Full text Link to item Cite

Stromal Fibroblasts Mediate Anti-PD-1 Resistance via MMP-9 and Dictate TGFβ Inhibitor Sequencing in Melanoma.

Journal Article Cancer Immunol Res · December 2018 Although anti-PD-1 therapy has improved clinical outcomes for select patients with advanced cancer, many patients exhibit either primary or adaptive resistance to checkpoint inhibitor immunotherapy. The role of the tumor stroma in the development of these ... Full text Open Access Link to item Cite

Endoglin interacts with VEGFR2 to promote angiogenesis.

Journal Article FASEB J · June 2018 Endoglin, a TGF-β coreceptor predominantly expressed in endothelial cells, plays an important role in vascular development and tumor-associated angiogenesis. However, the mechanism by which endoglin regulates angiogenesis, especially during tip cell format ... Full text Link to item Cite

Endoglin Mediates Vascular Maturation by Promoting Vascular Smooth Muscle Cell Migration and Spreading.

Journal Article Arterioscler Thromb Vasc Biol · June 2017 OBJECTIVE: Endoglin, a transforming growth factor-β superfamily coreceptor, is predominantly expressed in endothelial cells and has essential roles in vascular development. However, whether endoglin is also expressed in vascular smooth muscle cells (VSMCs) ... Full text Link to item Cite

Heparin-binding epidermal growth factor-like growth factor promotes neuroblastoma differentiation.

Journal Article FASEB J · May 2017 High-risk neuroblastoma is characterized by undifferentiated neuroblasts and low schwannian stroma content. The tumor stroma contributes to the suppression of tumor growth by releasing soluble factors that promote neuroblast differentiation. Here we identi ... Full text Link to item Cite

Phase I study of pazopanib plus TH-302 in advanced solid tumors.

Journal Article Cancer Chemother Pharmacol · March 2017 PURPOSE: To define the maximum tolerated dose (MTD), recommended phase II dose (RPTD), and assess safety and tolerability for the combination of pazopanib plus TH-302, an investigational hypoxia-activated prodrug (HAP), in adult patients with advanced soli ... Full text Link to item Cite

TGF-β-induced stromal CYR61 promotes resistance to gemcitabine in pancreatic ductal adenocarcinoma through downregulation of the nucleoside transporters hENT1 and hCNT3.

Journal Article Carcinogenesis · November 1, 2016 Pancreatic ductal adenocarcinoma (PDAC) is a lethal cancer in part due to inherent resistance to chemotherapy, including the first-line drug gemcitabine. Although low expression of the nucleoside transporters hENT1 and hCNT3 that mediate cellular uptake of ... Full text Link to item Cite

Dichotomous roles of TGF-β in human cancer.

Journal Article Biochem Soc Trans · October 15, 2016 Transforming growth factor-β (TGF-β) mediates numerous biological processes, including embryonic development and the maintenance of cellular homeostasis in a context-dependent manner. Consistent with its central role in maintaining cellular homeostasis, in ... Full text Link to item Cite

Abstract 1182: Heparin-binding epidermal growth factor-like growth factor is a pro-differentiating factor in neuroblastoma

Conference Cancer Research · July 15, 2016 AbstractNeuroblastoma is the most common cancer in infancy. Current therapies are only modestly effective; patients with high-risk disease have less than a 50% chance of survival. High-risk neuroblastoma is ... Full text Cite

An Automated High-throughput Array Microscope for Cancer Cell Mechanics.

Journal Article Sci Rep · June 6, 2016 Changes in cellular mechanical properties correlate with the progression of metastatic cancer along the epithelial-to-mesenchymal transition (EMT). Few high-throughput methodologies exist that measure cell compliance, which can be used to understand the im ... Full text Link to item Cite

Fibulin-3 is a novel TGF-β pathway inhibitor in the breast cancer microenvironment.

Journal Article Oncogene · November 5, 2015 Transforming growth factor-β (TGF-β) is an important regulator of breast cancer progression. However, how the breast cancer microenvironment regulates TGF-β signaling during breast cancer progression remains largely unknown. Here, we identified fibulin-3 a ... Full text Link to item Cite

TβRIII independently binds type I and type II TGF-β receptors to inhibit TGF-β signaling.

Journal Article Mol Biol Cell · October 1, 2015 Transforming growth factor-β (TGF-β) receptor oligomerization has important roles in signaling. Complex formation among type I and type II (TβRI and TβRII) TGF-β receptors is well characterized and is essential for signal transduction. However, studies on ... Full text Link to item Cite

Dalantercept

Journal Article Drugs of the Future · October 1, 2015 The TGF-b superfamily receptor activin receptor-like kinase 1 (ALK-1) has essential roles in regulating angiogenesis during development and homeostasis, as well as pathophysiological tumor angiogenesis. Dalantercept is a soluble chimeric protein composed o ... Full text Cite

Regulation of TGF-β receptor hetero-oligomerization and signaling by endoglin.

Journal Article Mol Biol Cell · September 1, 2015 Complex formation among transforming growth factor-β (TGF-β) receptors and its modulation by coreceptors represent an important level of regulation for TGF-β signaling. Oligomerization of ALK5 and the type II TGF-β receptor (TβRII) has been thoroughly inve ... Full text Link to item Cite

Angiotensin II stimulates canonical TGF-β signaling pathway through angiotensin type 1 receptor to induce granulation tissue contraction.

Conference J Mol Med (Berl) · March 2015 UNLABELLED: Hypertrophic scar contraction (HSc) is caused by granulation tissue contraction propagated by myofibroblast and fibroblast migration and contractility. Identifying the stimulants that promote migration and contractility is key to mitigating HSc ... Full text Link to item Cite

TGF-β regulates LARG and GEF-H1 during EMT to affect stiffening response to force and cell invasion.

Journal Article Mol Biol Cell · November 5, 2014 Recent studies implicate a role for cell mechanics in cancer progression. The epithelial-to-mesenchymal transition (EMT) regulates the detachment of cancer cells from the epithelium and facilitates their invasion into stromal tissue. Although classic EMT h ... Full text Link to item Cite

Effects of the combination of TRC105 and bevacizumab on endothelial cell biology.

Journal Article Invest New Drugs · October 2014 Endoglin, or CD105, is a cell membrane glycoprotein that is overexpressed on proliferating endothelial cells (EC), including those found in malignancies and choroidal neovascularization. Endoglin mediates the transition from quiescent endothelium, characte ... Full text Link to item Cite

Abstract 2674: Stroma biology identifies heparins as differentiating agents in neuroblastoma

Conference Cancer Research · October 1, 2014 AbstractThe neuroblastoma tumor stroma is thought to suppress neuroblast growth via release of soluble differentiating factors. Here we identify these factors and design a novel therapy based on their mechan ... Full text Cite

Ectodomain shedding of TβRIII is required for TβRIII-mediated suppression of TGF-β signaling and breast cancer migration and invasion.

Journal Article Mol Biol Cell · August 15, 2014 The type III transforming growth factor β (TGF-β) receptor (TβRIII), also known as betaglycan, is the most abundantly expressed TGF-β receptor. TβRIII suppresses breast cancer progression by inhibiting migration, invasion, metastasis, and angiogenesis. TβR ... Full text Link to item Cite

Role of TGF-β receptor III localization in polarity and breast cancer progression.

Journal Article Mol Biol Cell · August 1, 2014 The majority of breast cancers originate from the highly polarized luminal epithelial cells lining the breast ducts. However, cell polarity is often lost during breast cancer progression. The type III transforming growth factor-β cell surface receptor (TβR ... Full text Link to item Cite

Stromal heparan sulfate differentiates neuroblasts to suppress neuroblastoma growth.

Journal Article J Clin Invest · July 2014 Neuroblastoma prognosis is dependent on both the differentiation state and stromal content of the tumor. Neuroblastoma tumor stroma is thought to suppress neuroblast growth via release of soluble differentiating factors. Here, we identified critical growth ... Full text Link to item Cite

Heparan sulfate signaling in cancer.

Journal Article Trends Biochem Sci · June 2014 Heparan sulfate (HS) is a biopolymer consisting of variably sulfated repeating disaccharide units. The anticoagulant heparin is a highly sulfated intracellular variant of HS. HS has demonstrated roles in embryonic development, homeostasis, and human diseas ... Full text Link to item Cite

The balance of cell surface and soluble type III TGF-β receptor regulates BMP signaling in normal and cancerous mammary epithelial cells.

Journal Article Neoplasia · June 2014 Bone morphogenetic proteins (BMPs) are members of the TGF-β superfamily that are over-expressed in breast cancer, with context dependent effects on breast cancer pathogenesis. The type III TGF-β receptor (TβRIII) mediates BMP signaling. While TβRIII expres ... Full text Link to item Cite

Phase I study of dasatinib in combination with capecitabine, oxaliplatin and bevacizumab followed by an expanded cohort in previously untreated metastatic colorectal cancer.

Journal Article Invest New Drugs · April 2014 PURPOSE: Dasatinib inhibits src family kinases and has anti-angiogenic properties. We conducted a phase I study of dasatinib, capecitabine, oxaliplatin, and bevacizumab (CapeOx/bevacizumab), with an expansion cohort in metastatic colorectal cancer (CRC). M ... Full text Link to item Cite

Novel bone morphogenetic protein signaling through Smad2 and Smad3 to regulate cancer progression and development.

Journal Article FASEB J · March 2014 The bone morphogenetic protein (BMP) signaling pathways have important roles in embryonic development and cellular homeostasis, with aberrant BMP signaling resulting in a broad spectrum of human disease. We report that BMPs unexpectedly signal through the ... Full text Link to item Cite

Safety, pharmacokinetics, pharmacodynamics, and antitumor activity of dalantercept, an activin receptor-like kinase-1 ligand trap, in patients with advanced cancer.

Journal Article Clin Cancer Res · January 15, 2014 PURPOSE: The angiogenesis inhibitor dalantercept (formerly ACE-041) is a soluble form of activin receptor-like kinase-1 (ALK1) that prevents activation of endogenous ALK1 by bone morphogenetic protein-9 (BMP9) and BMP10 and exhibits antitumor activity in p ... Full text Link to item Cite

Abstract C61: Phase I Study of pazopanib in combination with the investigational hypoxia-targeted drug TH-302.

Journal Article Molecular Cancer Therapeutics · November 1, 2013 AbstractBackground: Preclinical data demonstrate anti-VEGF agents can induce hypoxia, which may mediate resistance and induce increased tumor invasiveness. TH-302 is an investigational hypoxia-targeted drug; ... Full text Cite

Type III TGF-β receptor promotes FGF2-mediated neuronal differentiation in neuroblastoma.

Journal Article J Clin Invest · November 2013 Growth factors and their receptors coordinate neuronal differentiation during development, yet their roles in the pediatric tumor neuroblastoma remain unclear. Comparison of mRNA from benign neuroblastic tumors and neuroblastomas revealed that expression o ... Full text Link to item Cite

Type III TGF-β receptor downregulation generates an immunotolerant tumor microenvironment.

Journal Article J Clin Invest · September 2013 Cancers subvert the host immune system to facilitate disease progression. These evolved immunosuppressive mechanisms are also implicated in circumventing immunotherapeutic strategies. Emerging data indicate that local tumor-associated DC populations exhibi ... Full text Open Access Link to item Cite

The type III TGFβ receptor regulates filopodia formation via a Cdc42-mediated IRSp53-N-WASP interaction in epithelial cells.

Journal Article Biochem J · August 15, 2013 Cell adhesion and migration are tightly controlled by regulated changes in the actin cytoskeleton. Previously we reported that the TGFβ (transforming growth factor β) superfamily co-receptor, TβRIII (type III TGFβ receptor; also known as βglycan), regulate ... Full text Link to item Cite

A phase I study of ABT-510 plus bevacizumab in advanced solid tumors.

Journal Article Cancer Med · June 2013 Targeting multiple regulators of tumor angiogenesis have the potential to improve treatment efficacy. Bevacizumab is a monoclonal antibody directed against vascular endothelial growth factor and ABT-510 is a synthetic analog of thrombospondin, an endogenou ... Full text Open Access Link to item Cite

Abstract 5041: The type III TGF-beta receptor promotes FGF2-mediated neuronal differentiation in neuroblastoma.

Conference Cancer Research · April 15, 2013 AbstractGrowth factors and their receptors coordinate neuronal differentiation during development, yet their roles in the pediatric tumor neuroblastoma remain unclear. Here we report that expression of type ... Full text Cite

TβRIII/β-arrestin2 regulates integrin α5β1 trafficking, function, and localization in epithelial cells.

Journal Article Oncogene · March 14, 2013 Featured Publication The type III TGF-β receptor (TβRIII) is a ubiquitous co-receptor for TGF-β superfamily ligands with roles in suppressing cancer progression, in part through suppressing cell motility. Here we demonstrate that TβRIII promotes epithelial cell adhesion to fib ... Full text Link to item Cite

Emerging roles of TGF-β co-receptors in human disease

Chapter · January 1, 2013 TGF-β signaling is both regulated and mediated by signaling co- receptors. Several TGF-β co-receptors have been identifi ed including endoglin (CD105), the type III TGF-β receptor (TβRIII, betaglycan), neuropilin-1/2, syndecan- 2, CD109, and LRP1. These co ... Full text Cite

A phase II study of capecitabine, oxaliplatin, and bevacizumab in the treatment of metastatic esophagogastric adenocarcinomas.

Journal Article Oncologist · 2013 BACKGROUND: Esophageal and gastric cancers often present at an advanced stage. Systemic chemotherapy is the mainstay of treatment, but survival with current regimens remains poor. We evaluated the safety, tolerability, and efficacy of the combination capec ... Full text Link to item Cite

Endoglin mediates fibronectin/α5β1 integrin and TGF-β pathway crosstalk in endothelial cells.

Journal Article EMBO J · October 3, 2012 Both the transforming growth factor β (TGF-β) and integrin signalling pathways have well-established roles in angiogenesis. However, how these pathways integrate to regulate angiogenesis is unknown. Here, we show that the extracellular matrix component, fi ... Full text Link to item Cite

Endoglin regulates PI3-kinase/Akt trafficking and signaling to alter endothelial capillary stability during angiogenesis.

Journal Article Mol Biol Cell · July 2012 Featured Publication Endoglin (CD105) is an endothelial-specific transforming growth factor β (TGF-β) coreceptor essential for angiogenesis and vascular homeostasis. Although endoglin dysfunction contributes to numerous vascular conditions, the mechanism of endoglin action rem ... Full text Link to item Cite

A phase I study of bevacizumab, everolimus and panitumumab in advanced solid tumors.

Journal Article Cancer Chemother Pharmacol · July 2012 PURPOSE: Preclinical data suggest concurrent inhibition of VEGF, mTOR and EGFR pathways may augment antitumor and antiangiogenic effects compared to inhibition of each pathway alone. This study evaluated the maximum tolerated dose/recommended phase II dose ... Full text Link to item Cite

Abstract 3035: Bone morphogenetic proteins signal through Smad2 and Smad3 to regulate cell migration and proliferation

Journal Article Cancer Research · April 15, 2012 AbstractThe TGF-β superfamily consists of a large number of growth factors, including transforming growth factor-β (TGF-β) and bone morphogenetic proteins (BMPs) that regulate cellular proliferation, differe ... Full text Cite

Endocardial cell epithelial-mesenchymal transformation requires Type III TGFβ receptor interaction with GIPC.

Journal Article Cell Signal · January 2012 An early event in heart valve formation is the epithelial-mesenchymal transformation (EMT) of a subpopulation of endothelial cells in specific regions of the heart tube, the endocardial cushions. The Type III TGFβ receptor (TGFβR3) is required for TGFβ2- o ... Full text Link to item Cite

Molecular characterization of the tumor-suppressive function of nischarin in breast cancer.

Journal Article J Natl Cancer Inst · October 19, 2011 BACKGROUND: Nischarin (encoded by NISCH), an α5 integrin-binding protein, has been identified as a regulator of breast cancer cell invasion. We hypothesized that it might be a tumor suppressor and were interested in its regulation. METHODS: We examined nis ... Full text Link to item Cite

A phase II study of oxaliplatin, dose-intense capecitabine, and high-dose bevacizumab in the treatment of metastatic colorectal cancer.

Journal Article Clin Colorectal Cancer · September 2011 BACKGROUND: This study was designed to determine the efficacy and tolerability of a novel 2-week regimen of capecitabine, oxaliplatin (OHP), and bevacizumab in patients with chemo-naive advanced colorectal cancer. PATIENTS AND METHODS: Nineteen patients wi ... Full text Link to item Cite

Mechanical stiffness grades metastatic potential in patient tumor cells and in cancer cell lines.

Journal Article Cancer Res · August 1, 2011 Featured Publication Cancer cells are defined by their ability to invade through the basement membrane, a critical step during metastasis. While increased secretion of proteases, which facilitates degradation of the basement membrane, and alterations in the cytoskeletal archit ... Full text Link to item Cite

Type III TGF-β receptor enhances colon cancer cell migration and anchorage-independent growth.

Journal Article Neoplasia · August 2011 The type III TGF-β receptor (TβRIII or betagylcan) is a TGF-β superfamily coreceptor with emerging roles in regulating TGF-β superfamily signaling and cancer progression. Alterations in TGF-β superfamily signaling are common in colon cancer; however, the r ... Full text Link to item Cite

Phase I study of dasatinib in combination with capecitabine, oxaliplatin, and bevacizumab followed by an expanded cohort in previously untreated metastatic colorectal cancer.

Journal Article J Clin Oncol · May 20, 2011 3586 Background: SRC is a non-receptor tyrosine kinase involved in normal and tumor cell signaling functions including cell proliferation, angiogenesis and survival. Dasatinib (D) is a potent inhibitor of SRC kinase activity. Preclinical data suggests the ... Link to item Cite

Role of the type III TGF-β receptor in modulating antitumor immunity during breast cancer progression.

Journal Article J Clin Oncol · May 20, 2011 10540 Background: We have shown that breast cancers downregulate the expression of the type III TGF-β receptor (TβRIII) tumor suppressor during tumor progression. Previous work has shown TβRIII to undergo ectodomain shedding, enabling the sequestration of ... Link to item Cite

The type III transforming growth factor-β receptor inhibits proliferation, migration, and adhesion in human myeloma cells.

Journal Article Mol Biol Cell · May 2011 Featured Publication Transforming growth factor-β (TGF-β) plays an important role in regulating hematopoiesis, inhibiting proliferation while stimulating differentiation when appropriate. We previously demonstrated that the type III TGF-β receptor (TβRIII, or betaglycan) serve ... Full text Link to item Cite

Phase I study of dasatinib in combination with capecitabine, oxaliplatin, and bevacizumab followed by an expanded cohort in previously untreated metastatic colorectal cancer.

Journal Article J Clin Oncol · February 2011 513 Background: SRC is a non-receptor tyrosine kinase involved in normal and tumor cell signaling functions including cell proliferation, angiogenesis and survival. Dasatinib (D) is a potent inhibitor of SRC kinase activity. Preclinical data suggests the a ... Link to item Cite

A phase I study of bevacizumab (B) in combination with everolimus (E) and erlotinib (E) in advanced cancer (BEE).

Journal Article Cancer Chemother Pharmacol · February 2011 PURPOSE: VEGF, mTOR, and EGFR inhibitors have demonstrated anti-tumor and anti-angiogenic effects alone and in combination with each other. This study evaluated the safety, tolerability, and pharmacokinetics of bevacizumab, everolimus, and erlotinib combin ... Full text Link to item Cite

BMP-2 and TGFβ2 shared pathways regulate endocardial cell transformation.

Journal Article Cells Tissues Organs · 2011 Valvular heart disease is a major cause of mortality and morbidity. Revealing the cellular processes and molecules that regulate valve formation and remodeling is required to develop effective therapies. A key step in valve formation during heart developme ... Full text Link to item Cite

A phase II trial of bevacizumab plus everolimus for patients with refractory metastatic colorectal cancer.

Journal Article Oncologist · 2011 PURPOSE: For patients with metastatic colorectal cancer (mCRC), no standard therapy exists after progression on 5-fluorouracil, oxaliplatin, irinotecan, bevacizumab, and cetuximab or panitumumab. Preclinical data demonstrated that combined vascular endothe ... Full text Link to item Cite

A phase II study of capecitabine, oxaliplatin, bevacizumab and cetuximab in the treatment of metastatic colorectal cancer.

Journal Article Anticancer Res · January 2011 AIM: This study was designed to determine the efficacy and tolerability of capecitabine, oxaliplatin and bevacizumab in combination with cetuximab as first-line therapy for advanced colorectal cancer. PATIENTS AND METHODS: Patients with previously untreate ... Link to item Cite

Deep sequencing of the small RNA transcriptome of normal and malignant human B cells identifies hundreds of novel microRNAs.

Journal Article Blood · December 2, 2010 A role for microRNA (miRNA) has been recognized in nearly every biologic system examined thus far. A complete delineation of their role must be preceded by the identification of all miRNAs present in any system. We elucidated the complete small RNA transcr ... Full text Link to item Cite

Roles for the type III TGF-beta receptor in human cancer.

Journal Article Cell Signal · August 2010 Transforming growth factor beta (TGF-beta) superfamily ligands have important roles in regulating cellular homeostasis, embryonic development, differentiation, proliferation, immune surveillance, angiogenesis, motility, and apoptosis in a cell type and con ... Full text Link to item Cite

Loss of type III transforming growth factor-beta receptor expression is due to methylation silencing of the transcription factor GATA3 in renal cell carcinoma.

Journal Article Oncogene · May 20, 2010 Loss of transforming growth factor-beta receptor III (TbetaRIII) correlates with loss of transforming growth factor-beta (TGF-beta) responsiveness and suggests a role for dysregulated TGF-beta signaling in clear cell renal cell carcinoma (ccRCC) progressio ... Full text Link to item Cite

Abstract 3971: The type III tgf-β receptor mediates bmp signaling in normal and cancerous mammary epithelial cells

Journal Article Cancer Research · April 15, 2010 AbstractBMP signaling has been shown to enhance breast cancer invasion and bone metastasis, while inhibition of BMP signaling abrogates bone metastasis in an in vivo model. The type III TGF-β receptor (TβRII ... Full text Cite

Gfi-1B controls human erythroid and megakaryocytic differentiation by regulating TGF-beta signaling at the bipotent erythro-megakaryocytic progenitor stage.

Journal Article Blood · April 8, 2010 Growth factor independence-1B (Gfi-1B) is a transcriptional repressor essential for erythropoiesis and megakaryopoiesis. Targeted gene disruption of GFI1B in mice leads to embryonic lethality resulting from failure to produce definitive erythrocytes, hinde ... Full text Link to item Cite

A phase I dose-escalation study of imatinib mesylate (Gleevec/STI571) plus capecitabine (Xeloda) in advanced solid tumors.

Journal Article Anticancer Res · April 2010 UNLABELLED: The aim of this study was to determine the maximally tolerated dose, recommended phase II dose and toxicity profile of capecitabine plus imatinib mesylate combination. PATIENTS AND METHODS: Twenty-four patients with advanced solid tumors were t ... Link to item Cite

ALK5 phosphorylation of the endoglin cytoplasmic domain regulates Smad1/5/8 signaling and endothelial cell migration.

Journal Article Carcinogenesis · March 2010 Endoglin, an endothelial cell-specific transforming growth factor-beta (TGF-beta) superfamily coreceptor, has an essential role in angiogenesis. Endoglin-null mice have an embryonic lethal phenotype due to defects in angiogenesis and mutations in endoglin ... Full text Link to item Cite

The type III TGF-beta receptor suppresses breast cancer progression through GIPC-mediated inhibition of TGF-beta signaling.

Journal Article Carcinogenesis · February 2010 Loss of expression of the type III transforming growth factor-beta receptor (TbetaRIII or betaglycan), a transforming growth factor-beta (TGF-beta) superfamily co-receptor, is common in human breast cancers. TbetaRIII suppresses cancer progression in vivo ... Full text Link to item Cite

Phase I dose escalation study of gemcitabine plus irinotecan in advanced solid tumors.

Journal Article Anticancer Res · December 2009 AIM: To determine the maximally tolerated dose (MTD), recommended phase II dose (RPTD) and toxicity profile of gemcitabine plus irinotecan combination. PATIENTS AND METHODS: Thirty-nine evaluable patients with advanced solid tumors were treated with gemcit ... Link to item Cite

Casein kinase 2beta as a novel enhancer of activin-like receptor-1 signaling.

Journal Article FASEB J · November 2009 Featured Publication ALK-1 is a transforming growth factor beta (TGF-beta) superfamily receptor that is predominantly expressed in endothelial cells and is essential for angiogenesis, as demonstrated by the embryonic lethal phentoype when targeted for deletion in mice and its ... Full text Link to item Cite

Proteoglycan signaling co-receptors: roles in cell adhesion, migration and invasion.

Journal Article Cell Signal · November 2009 Signaling co-receptors are diverse, multifunctional components of most major signaling pathways, with roles in mediating and regulating signaling in both physiological and pathophysiological circumstances. Many of these signaling co-receptors, including CD ... Full text Link to item Cite

The transforming growth factor-beta type III receptor mediates distinct subcellular trafficking and downstream signaling of activin-like kinase (ALK)3 and ALK6 receptors.

Journal Article Mol Biol Cell · October 2009 Featured Publication Bone morphogenetic proteins (BMPs) signal through the BMP type I and type II receptors to regulate cellular processes, including embryonic development. The type I BMP receptors activin-like kinase (ALK)3 and ALK6 share a high degree of homology, yet posses ... Full text Link to item Cite

The type III TGFbeta receptor regulates directional migration: new tricks for an old dog.

Journal Article Cell Cycle · October 1, 2009 The type III transforming growth factor beta (TGFbeta) receptor (T beta RIII or betaglycan) is a TGFbeta superfamily co-receptor. Loss of T beta RIII expression occurs in a broad spectrum of human cancers including cancers of the breast, kidney, lung, ovar ... Full text Link to item Cite

The type III transforming growth factor-beta receptor negatively regulates nuclear factor kappa B signaling through its interaction with beta-arrestin2.

Journal Article Carcinogenesis · August 2009 Transforming growth factor-beta (TGF-beta) increases or decreases nuclear factor kappa B (NFkappaB) signaling in a context-dependent manner through mechanisms that remain to be defined. The type III transforming growth factor-beta receptor (TbetaRIII) is a ... Full text Link to item Cite

Bevacizumab (B) plus everolimus (E) in refractory metastatic colorectal cancer (mCRC).

Journal Article J Clin Oncol · May 20, 2009 4080 Background: For patients (pts) with mCRC, no standard therapy exists after progression on 5-FU, oxaliplatin, irinotecan, bevacizumab, and/or cetuximab/panitumumab. Preclinical data demonstrate combined VEGF and mTOR inhibition has greater anti-angioge ... Link to item Cite

Bevacizumab (B) plus everolimus (E) and panitumumab (P) in refractory advanced solid tumors.

Journal Article J Clin Oncol · May 20, 2009 3551 Background: In preclinical models, VEGF, mTOR, and EGFR inhibitors have anti-tumor and anti-angiogenesis effects as monotherapies and in combination. B inhibits VEGF; E inhibits mTOR; P inhibits EGFR. There is also potential for interaction between th ... Link to item Cite

The type III TGF-beta receptor regulates epithelial and cancer cell migration through beta-arrestin2-mediated activation of Cdc42.

Journal Article Proc Natl Acad Sci U S A · May 19, 2009 Featured Publication Loss of expression of the TGF-beta superfamily coreceptor, the type III TGF-beta receptor (TbetaRIII or betaglycan), occurs in a broad spectrum of human cancers including breast, lung, ovarian, pancreatic, prostate, and renal cell cancer. TbetaRIII suppres ... Full text Link to item Cite

Bone morphogenetic proteins induce pancreatic cancer cell invasiveness through a Smad1-dependent mechanism that involves matrix metalloproteinase-2.

Journal Article Carcinogenesis · February 2009 Bone morphogenetic proteins (BMPs) have an emerging role in human cancers. Here we demonstrate that the BMP-signaling pathway is intact and functional in human pancreatic cancer cells, with several BMP signaling components and transcriptional targets upreg ... Full text Link to item Cite

Endocytosis of the type III transforming growth factor-beta (TGF-beta) receptor through the clathrin-independent/lipid raft pathway regulates TGF-beta signaling and receptor down-regulation.

Journal Article J Biol Chem · December 12, 2008 Featured Publication Transforming growth factor-beta (TGF-beta) signals through three highly conserved cell surface receptors, the type III TGF-beta receptor (T beta RIII), the type II TGF-beta receptor (T beta RII), and the type I TGF-beta receptor (T beta RI) to regulate div ... Full text Link to item Cite

Endoglin promotes transforming growth factor beta-mediated Smad 1/5/8 signaling and inhibits endothelial cell migration through its association with GIPC.

Journal Article J Biol Chem · November 21, 2008 Featured Publication Transforming growth factor beta (TGF-beta) signals through two distinct pathways to regulate endothelial cell proliferation, migration, and angiogenesis, the ALK-1/Smad 1/5/8 and ALK-5/Smad2/3 pathways. Endoglin is a co-receptor predominantly expressed in ... Full text Link to item Cite

Expression of the type III TGF-beta receptor is negatively regulated by TGF-beta.

Journal Article Carcinogenesis · May 2008 The type III transforming growth factor-beta receptor (TbetaRIII or betaglycan) is a ubiquitously expressed transforming growth factor-beta (TGF-beta) superfamily coreceptor with essential roles in embryonic development. Recent studies have defined a role ... Full text Link to item Cite

Role of transforming growth factor-beta superfamily signaling pathways in human disease.

Journal Article Biochim Biophys Acta · April 2008 Transforming growth factor beta (TGF-beta) superfamily signaling pathways are ubiquitous and essential regulators of cellular processes including proliferation, differentiation, migration, and survival, as well as physiological processes, including embryon ... Full text Link to item Cite

Bone morphogenetic proteins signal through the transforming growth factor-beta type III receptor.

Journal Article J Biol Chem · March 21, 2008 Featured Publication The bone morphogenetic protein (BMP) family, the largest subfamily of the structurally conserved transforming growth factor-beta (TGF-beta) superfamily of growth factors, are multifunctional regulators of development, proliferation, and differentiation. Th ... Full text Link to item Cite

TbetaRIII suppresses non-small cell lung cancer invasiveness and tumorigenicity.

Journal Article Carcinogenesis · March 2008 The transforming growth factor-beta (TGF-beta) superfamily has essential roles in lung development, regulating cell proliferation, branching morphogenesis, differentiation and apoptosis. Although most lung cancers become resistant to the tumor suppressor e ... Full text Link to item Cite

Loss of type III transforming growth factor beta receptor expression increases motility and invasiveness associated with epithelial to mesenchymal transition during pancreatic cancer progression.

Journal Article Carcinogenesis · February 2008 Epithelial to mesenchymal transitions (EMTs) contribute to increases in cellular motility and invasiveness during embryonic development and tumorigenesis. The transforming growth factor beta (TGF-beta) signaling pathway is a key regulator of EMT. The TGF-b ... Full text Link to item Cite

The type III TGF-beta receptor signals through both Smad3 and the p38 MAP kinase pathways to contribute to inhibition of cell proliferation.

Journal Article Carcinogenesis · December 2007 Transforming growth factor beta (TGFbeta) has an important role as a negative regulator of cellular proliferation. The type III transforming growth factor beta receptor (TbetaRIII) has an emerging role as both a TGFbeta superfamily co-receptor and in media ... Full text Link to item Cite

The interaction of endoglin with beta-arrestin2 regulates transforming growth factor-beta-mediated ERK activation and migration in endothelial cells.

Journal Article J Biol Chem · July 20, 2007 Featured Publication In endothelial cells, transforming growth factor beta (TGF-beta) signals through two distinct pathways to regulate endothelial cell proliferation and migration, the ALK-1/Smads 1/5/8 pathway and the ALK-5/Smads 2/3 pathway. TGF-beta signaling through these ... Full text Link to item Cite

Loss of betaglycan expression in ovarian cancer: role in motility and invasion.

Journal Article Cancer Res · June 1, 2007 Featured Publication The transforming growth factor-beta (TGF-beta) superfamily members, TGF-beta, activin, and inhibin, all have prominent roles in regulating normal ovarian function. Betaglycan, or the type III TGF-beta receptor, is a coreceptor that regulates TGF-beta, acti ... Full text Link to item Cite

Bevacizumab, oxaliplatin, and capecitabine with radiation therapy in rectal cancer: Phase I trial results.

Journal Article Int J Radiat Oncol Biol Phys · June 1, 2007 PURPOSE: The overexpression of vascular endothelial growth factor (VEGF) is associated with poor outcomes in colorectal cancer patients. Bevacizumab, a VEGF inhibitor, enhances the effects of chemotherapy and radiation therapy on tumor cytotoxicity in prec ... Full text Link to item Cite

A Phase I study of capecitabine, carboplatin, and paclitaxel with external beam radiation therapy for esophageal carcinoma.

Journal Article Int J Radiat Oncol Biol Phys · March 15, 2007 PURPOSE: Concurrent chemotherapy and radiation therapy (RT) are used to treat patients with esophageal cancer. The optimal combination of chemotherapeutic agents with RT is undefined. We evaluated a combination of capecitabine, carboplatin, and paclitaxel ... Full text Link to item Cite

The type III transforming growth factor-beta receptor as a novel tumor suppressor gene in prostate cancer.

Journal Article Cancer Res · February 1, 2007 Featured Publication The transforming growth factor-beta (TGF-beta) signaling pathway has an important role in regulating normal prostate epithelium, inhibiting proliferation, differentiation, and both androgen deprivation-induced and androgen-independent apoptosis. During pro ... Full text Link to item Cite

The type III TGF-beta receptor suppresses breast cancer progression.

Journal Article J Clin Invest · January 2007 Featured Publication The TGF-beta signaling pathway has a complex role in regulating mammary carcinogenesis. Here we demonstrate that the type III TGF-beta receptor (TbetaRIII, or betaglycan), a ubiquitously expressed TGF-beta coreceptor, regulated breast cancer progression an ... Full text Link to item Cite

Role of transforming growth factor-beta in hematologic malignancies.

Journal Article Blood · June 15, 2006 The transforming growth factor-beta (TGF-beta) signaling pathway is an essential regulator of cellular processes, including proliferation, differentiation, migration, and cell survival. During hematopoiesis, the TGF-beta signaling pathway is a potent negat ... Full text Link to item Cite

Increased toxicity with gefitinib, capecitabine, and radiation therapy in pancreatic and rectal cancer: phase I trial results.

Journal Article J Clin Oncol · February 1, 2006 PURPOSE: Overexpression of epidermal growth factor receptor (EGFR) has been associated with aggressive tumor phenotypes, chemotherapy, and radiation resistance, as well as poor survival in preclinical and clinical models. The EGFR inhibitor gefitinib poten ... Full text Link to item Cite

Cell-surface co-receptors: emerging roles in signaling and human disease.

Journal Article Trends Biochem Sci · November 2005 Extracellular signals are transmitted to cells through two classes of cell-surface receptors: signaling receptors that directly transduce signals and signaling co-receptors that bind ligand but that, traditionally, have not been thought to signal directly. ... Full text Link to item Cite

Role of transforming growth factor Beta in human cancer.

Journal Article J Clin Oncol · March 20, 2005 Featured Publication Transforming growth factor beta (TGF-beta) is a ubiquitous and essential regulator of cellular and physiologic processes including proliferation, differentiation, migration, cell survival, angiogenesis, and immunosurveillance. Alterations in the TGF-beta s ... Full text Link to item Cite

Significance of histological response to preoperative chemoradiotherapy for pancreatic cancer.

Journal Article Ann Surg Oncol · March 2005 BACKGROUND: Neoadjuvant (preoperative) chemoradiotherapy (CRT) for pancreatic cancer offers theoretical advantages over the standard approach of surgery followed by adjuvant CRT. We hypothesized that histological responses to CRT would be significant progn ... Full text Link to item Cite

Development of human protein reference database as an initial platform for approaching systems biology in humans.

Journal Article Genome Res · October 2003 Human Protein Reference Database (HPRD) is an object database that integrates a wealth of information relevant to the function of human proteins in health and disease. Data pertaining to thousands of protein-protein interactions, posttranslational modifica ... Full text Link to item Cite

Beta-arrestin 2 mediates endocytosis of type III TGF-beta receptor and down-regulation of its signaling.

Journal Article Science · September 5, 2003 Featured Publication beta-Arrestins bind to activated seven transmembrane-spanning (7TMS) receptors (G protein-coupled receptors) after the receptors are phosphorylated by G protein-coupled receptor kinases (GRKs), thereby regulating their signaling and internalization. Here, ... Full text Link to item Cite

Inhibiting the TGF-beta signalling pathway as a means of cancer immunotherapy.

Journal Article Expert Opin Biol Ther · April 2003 Cancers have developed numerous mechanisms for escaping the immune response, either by successfully evading a fully functional immune system or by actively suppressing the immune system so that they are no longer recognised or effectively eliminated. Curre ... Full text Link to item Cite

Regulation of ALK-1 signaling by the nuclear receptor LXRbeta.

Journal Article J Biol Chem · December 27, 2002 The transforming growth factor beta (TGF-beta) receptor, ALK-1, is expressed specifically on endothelial cells and is essential for angiogenesis, as demonstrated by its targeted deletion in mice and its mutation in the human disease hereditary hemorrhagic ... Full text Link to item Cite

Context-specific effects of fibulin-5 (DANCE/EVEC) on cell proliferation, motility, and invasion. Fibulin-5 is induced by transforming growth factor-beta and affects protein kinase cascades.

Journal Article J Biol Chem · July 26, 2002 Fibulin-5 (FBLN-5; also known as DANCE or EVEC) is an integrin-binding extracellular matrix protein that mediates endothelial cell adhesion; it is also a calcium-dependent elastin-binding protein that scaffolds cells to elastic fibers, thereby preventing e ... Full text Link to item Cite

A novel mechanism for regulating transforming growth factor beta (TGF-beta) signaling. Functional modulation of type III TGF-beta receptor expression through interaction with the PDZ domain protein, GIPC.

Journal Article J Biol Chem · October 26, 2001 Transforming growth factor beta (TGF-beta) mediates its biological effects through three high-affinity cell surface receptors, the TGF-beta type I, type II, and type III receptors, and the Smad family of transcription factors. Although the functions of the ... Full text Link to item Cite

Functional roles for the cytoplasmic domain of the type III transforming growth factor beta receptor in regulating transforming growth factor beta signaling.

Journal Article J Biol Chem · July 6, 2001 Transforming growth factor beta (TGF-beta) signals through three high affinity cell surface receptors, TGF-beta type I, type II, and type III receptors. The type III receptor, also known as betaglycan, binds to the type II receptor and is thought to act so ... Full text Link to item Cite

The p53 tumor suppressor gene in head and neck cancer

Journal Article Current Opinion in Otolaryngology and Head and Neck Surgery · May 19, 1998 Recent advances in recombinant DNA technology have allowed additional insight into the pathogenesis of cancer and may supply new tools to predict the course of disease and provide new methods of treatment. Research into the mutations or deletions of the p5 ... Full text Cite

Phosphorylation specificities of protein kinase C isozymes for bovine cardiac troponin I and troponin T and sites within these proteins and regulation of myofilament properties.

Journal Article J Biol Chem · September 20, 1996 Protein kinase C (PKC) isozymes alpha, delta, epsilon, and zeta, shown to be expressed in adult rat cardiomyocytes, displayed distinct substrate specificities in phosphorylating troponin I and troponin T subunits in the bovine cardiac troponin complex. Thu ... Full text Link to item Cite

Protein kinase C beta II specifically binds to and is activated by F-actin.

Journal Article J Biol Chem · June 28, 1996 The two most closely related isoenzymes of protein kinase C (PKC), PKC betaI and betaII, are distinct but highly homologous isoenzymes derived via alternative splicing of the same gene product. In this study, PKC betaII, but not PKC betaI, translocated to ... Full text Link to item Cite

Specific interactions of the protein kinase C beta isoenzymes

Conference MOLECULAR BIOLOGY OF THE CELL · 1996 Cite

Protein kinase C isoenzymes: regulation and function.

Journal Article Cancer Surv · 1996 PKC is composed of an ever growing family of lipid dependent serine/threonine protein kinases. Collectively, these isoenzymes are known to mediate critical roles in signal transduction, tumour promotion and cell regulation. PKCs appear to function as switc ... Link to item Cite

Arachidonic acid and free fatty acids as second messengers and the role of protein kinase C.

Journal Article Cell Signal · March 1995 In addition to serving as the precursor to a plethora of eicosanoids and other bioactive molecules, arachidonate may function as a bona fide second messenger. A number of studies have documented the ability of arachidonate to regulate the function of multi ... Full text Link to item Cite

Protein kinase C: cellular target of the second messenger arachidonic acid?

Journal Article Prostaglandins Leukot Essent Fatty Acids · 1995 Full text Link to item Cite

Regulation of protein kinase C and role in cancer biology.

Journal Article Cancer Metastasis Rev · December 1994 Protein kinase C (PKC) is a family of closely related lipid-dependent and diacyglycerol-activated isoenzymes known to play an important role in the signal transduction pathways involved in hormone release, mitogenesis and tumor promotion. Reversible activa ... Full text Link to item Cite

Identification of a defect in the phospholipase D/diacylglycerol pathway in cellular senescence.

Journal Article J Biol Chem · October 21, 1994 Normal cells become senescent in culture after a limited number of population doublings becoming unable to respond to mitogens. This raises the possibility of defects in mitogenic signaling pathways in cellular senescence. In contrast to young human diploi ... Link to item Cite

Specific role for protein kinase C beta in cell differentiation.

Journal Article Cell Growth Differ · April 1994 A critical role for protein kinase C (PKC) in signal transduction events has been well established. On the other hand, emerging evidence also suggests a role for regulation of PKC levels in mediating long term cellular functions. In human leukemia cell lin ... Link to item Cite

Identification, partial purification, and characterization of a novel phospholipid-dependent and fatty acid-activated protein kinase from human platelets.

Journal Article J Biol Chem · April 1, 1994 A novel lipid-dependent protein kinase in human platelets was partially purified and characterized. This enzyme was calcium-independent and was selective for phosphatidic acid as a cofactor/activator with initial activation observed at approximately 2 mol ... Link to item Cite

Selective regulation of expression of protein kinase C beta isoenzymes occurs via alternative splicing.

Journal Article J Biol Chem · May 15, 1993 The mechanisms involved in regulating the selective expression of protein kinase C (PKC) isoenzymes are poorly understood. Two human B lymphoblastoid cell lines, IM-9 and BJA-B, exhibited differential expression of the two alternatively spliced products of ... Link to item Cite

Selective regulation of protein kinase C isoenzymes by oleic acid in human platelets.

Journal Article J Biol Chem · March 5, 1993 Cis-unsaturated fatty acids activate soluble protein kinase C (PKC) in vitro and in intact platelets. The following studies were conducted to determine the effects of oleate on individual isoenzymes of PKC in human platelets. Human platelets were found to ... Link to item Cite

Selective regulation of expression of protein kinase C (PKC) isoenzymes in multidrug-resistant MCF-7 cells. Functional significance of enhanced expression of PKC alpha.

Journal Article J Biol Chem · January 5, 1993 The multidrug resistance (MDR) phenotype induces cross-resistance to many chemotherapeutic agents in cancer cells. Protein kinase C (PKC) has been implicated in the regulation of the MDR phenotype. In order to determine the role of specific PKC isoenzymes ... Link to item Cite

Cloning and characterization of the major promoter of the human protein kinase C beta gene. Regulation by phorbol esters.

Journal Article J Biol Chem · October 15, 1992 The expression of the beta isoenzyme for protein kinase C is regulated developmentally and in response to inducers of cell differentiation (such as phorbol esters and 1 alpha,25-dihydroxyvitamin D3). The 5' segment of the gene for protein kinase C beta was ... Link to item Cite

Activation of protein kinase C by oleic acid. Determination and analysis of inhibition by detergent micelles and physiologic membranes: requirement for free oleate.

Journal Article J Biol Chem · February 25, 1992 Sodium oleate is able to activate soluble protein kinase C (Murakami, K., Chan, S. Y., and Routtenberg, A. (1986) J. Biol. Chem. 261, 15424-15429) but is unable to activate membrane-bound enzyme (El Touny, S., Khan, W., and Hannun, Y. (1990) J. Biol. Chem. ... Link to item Cite

Conformational studies of the nucleic acid binding sites for Xenopus transcription factor IIIA.

Journal Article J Biol Chem · February 15, 1991 The CD spectrum of a restriction fragment that contains a single copy of a Xenopus borealis somatic 5 S rRNA gene, like those of two smaller fragments from the binding site for transcription factor IIIA (TFIIIA), is that of B-form DNA. Under dehydrating co ... Link to item Cite