Scholars@Duke
Ann Marie Pendergast

Ann Marie Pendergast

Anthony R. Means Cancer Biology Distinguished Professor
Pharmacology & Cancer Biology
ann.pendergast@duke.edu
Duke Box 3813, Durham, NC 27710
C233A Lev Sci Res Ctr, Durham, NC 27708

Selected Publications

PKN2 Is a Dependency of the Mesenchymal-like Cancer Cell State.

Journal Article Cancer Discov · March 3, 2025 Cancer cells exploit a mesenchymal-like transcriptional state (MLS) to survive drug treatments. Although the MLS is well characterized, few therapeutic vulnerabilities targeting this program have been identified. In this study, we systematically identify t ... Full text Link to item Cite

Activation of KrasG12D in Subset of Alveolar Type II Cells Enhances Cellular Plasticity in Lung Adenocarcinoma.

Journal Article Cancer Res Commun · November 24, 2023 UNLABELLED: We have previously identified alveolar type II cell as the cell-of-origin of KrasG12D-induced lung adenocarcinoma using cell lineage-specific inducible Cre mouse models. Using gain-of-function and loss-of-function genetic models, we discovered ... Full text Link to item Cite

Multi-Functional Regulation by YAP/TAZ Signaling Networks in Tumor Progression and Metastasis.

Journal Article Cancers (Basel) · September 24, 2023 The Hippo pathway transcriptional co-activators, YES-associated protein (YAP) and Transcriptional Co-Activator with PDZ Binding Motif (TAZ), have both been linked to tumor progression and metastasis. These two proteins possess overlapping and distinct func ... Full text Link to item Cite

ABL kinases regulate the stabilization of HIF-1α and MYC through CPSF1.

Journal Article Proceedings of the National Academy of Sciences of the United States of America · April 2023 The hypoxia-inducible factor 1-α (HIF-1α) enables cells to adapt and respond to hypoxia (Hx), and the activity of this transcription factor is regulated by several oncogenic signals and cellular stressors. While the pathways controlling normoxic degradatio ... Full text Open Access Cite

ABL1 and ABL2 promote medulloblastoma leptomeningeal dissemination.

Journal Article Neurooncol Adv · 2023 BACKGROUND: Medulloblastoma is the most common malignant pediatric brain tumor, and leptomeningeal dissemination (LMD) of medulloblastoma both portends a poorer prognosis at diagnosis and is incurable at recurrence. The biological mechanisms underlying LMD ... Full text Link to item Cite

Multi-apical polarity of alveolar stem cells and their dynamics during lung development and regeneration.

Journal Article iScience · October 21, 2022 Epithelial cells of diverse tissues are characterized by the presence of a single apical domain. In the lung, electron microscopy studies have suggested that alveolar type-2 epithelial cells (AT2s) en face multiple alveolar sacs. However, apical and basola ... Full text Open Access Link to item Cite

ABL kinases regulate translation in HER2+ cells through Y-box-binding protein 1 to facilitate colonization of the brain.

Journal Article Cell Rep · August 30, 2022 Patients with human epidermal growth factor receptor 2-positive (HER2+/ERBB2) breast cancer often present with brain metastasis. HER2-targeted therapies have not been successful to treat brain metastases in part due to poor blood-brain barrier (BBB) penetr ... Full text Link to item Cite

ABL allosteric inhibitors synergize with statins to enhance apoptosis of metastatic lung cancer cells.

Journal Article Cell Rep · October 26, 2021 Targeting mitochondrial metabolism has emerged as a treatment option for cancer patients. The ABL tyrosine kinases promote metastasis, and enhanced ABL signaling is associated with a poor prognosis in lung adenocarcinoma patients. Here we show that ABL kin ... Full text Link to item Cite

Role of the ABL tyrosine kinases in the epithelial-mesenchymal transition and the metastatic cascade.

Journal Article Cell Commun Signal · May 22, 2021 The ABL kinases, ABL1 and ABL2, promote tumor progression and metastasis in various solid tumors. Recent reports have shown that ABL kinases have increased expression and/or activity in solid tumors and that ABL inactivation impairs metastasis. The therape ... Full text Link to item Cite

Salting the Soil: Targeting the Microenvironment of Brain Metastases.

Journal Article Mol Cancer Ther · March 2021 Paget's "seed and soil" hypothesis of metastatic spread has acted as a foundation of the field for over a century, with continued evolution as mechanisms of the process have been elucidated. The central nervous system (CNS) presents a unique soil through t ... Full text Link to item Cite

The ABL2 kinase regulates an HSF1-dependent transcriptional program required for lung adenocarcinoma brain metastasis.

Journal Article Proc Natl Acad Sci U S A · December 29, 2020 Brain metastases are the most common intracranial tumors in adults and are associated with increased patient morbidity and mortality. Limited therapeutic options are currently available for the treatment of brain metastasis. Here, we report on the discover ... Full text Link to item Cite

Mesenchymal stem cells promote metastasis through activation of an ABL-MMP9 signaling axis in lung cancer cells.

Journal Article PLoS One · 2020 Mesenchymal stem cells (MSCs) are recruited and activated by solid tumors and play a role in tumor progression and metastasis. Here we show that MSCs promote metastasis in a panel of non-small cell lung cancer (NSCLC) cells. MSCs elicit transcriptional alt ... Full text Link to item Cite

A TAZ-AXL-ABL2 Feed-Forward Signaling Axis Promotes Lung Adenocarcinoma Brain Metastasis.

Journal Article Cell Rep · December 10, 2019 Brain metastases are a common consequence of advanced lung cancer, resulting in cranial neuropathies and increased mortality. Currently, there are no effective therapies to treat brain metastases due to a lack of actionable targets and a failure of systemi ... Full text Link to item Cite

The Evolving Modern Management of Brain Metastasis.

Journal Article Clin Cancer Res · November 15, 2019 The incidence of brain metastases is increasing as cancer therapies improve and patients live longer, providing new challenges to the multidisciplinary teams that care for these patients. Brain metastatic cancer cells possess unique characteristics that al ... Full text Link to item Cite

Correction: ABL kinase inhibition sensitizes primary lung adenocarcinomas to chemotherapy by promoting tumor cell differentiation (Oncotarget (2019) 10 (1874-1886) DOI: 10.18632/oncotarget.26740)

Journal Article Oncotarget · October 1, 2019 This article has been corrected: In Figure 2D, the panel for the loading control should be labeled 'tubulin', not 'GAPD.' We have corrected the legend to Figure 2D by updating this sentence: "Phospho-CrkL is a marker for Abl kinase activity while a-tubulin ... Cite

ABL kinase inhibition sensitizes primary lung adenocarcinomas to chemotherapy by promoting tumor cell differentiation.

Journal Article Oncotarget · March 8, 2019 Lung cancer is the leading cause of cancer mortality in the United States, with an overall five-year survival rate of ~16%. Non-small cell lung cancer (NSCLC) accounts for ~80% of all lung cancer cases, and the majority (40%) of these are adenocarcinomas. ... Full text Link to item Cite

ABL kinase inhibition promotes lung regeneration through expansion of an SCGB1A1+ SPC+ cell population following bacterial pneumonia.

Journal Article Proc Natl Acad Sci U S A · January 29, 2019 Current therapeutic interventions for the treatment of respiratory infections are hampered by the evolution of multidrug resistance in pathogens as well as the lack of effective cellular targets. Despite the identification of multiple region-specific lung ... Full text Link to item Cite

Inactivation of ABL kinases suppresses non-small cell lung cancer metastasis.

Journal Article JCI Insight · December 22, 2016 Current therapies to treat non-small cell lung carcinoma (NSCLC) have proven ineffective owing to transient, variable, and incomplete responses. Here we show that ABL kinases, ABL1 and ABL2, promote metastasis of lung cancer cells harboring EGFR or KRAS mu ... Full text Link to item Cite

Reciprocal stabilization of ABL and TAZ regulates osteoblastogenesis through transcription factor RUNX2.

Journal Article J Clin Invest · December 1, 2016 Cellular identity in metazoan organisms is frequently established through lineage-specifying transcription factors, which control their own expression through transcriptional positive feedback, while antagonizing the developmental networks of competing lin ... Full text Link to item Cite

ABL kinases promote breast cancer osteolytic metastasis by modulating tumor-bone interactions through TAZ and STAT5 signaling.

Journal Article Sci Signal · February 2, 2016 Bone metastases occur in up to 70% of advanced breast cancer. For most patients with breast cancer, bone metastases are predominantly osteolytic. Interactions between tumor cells and stromal cells in the bone microenvironment drive osteolytic bone metastas ... Full text Link to item Cite

Multifunctional Abl kinases in health and disease.

Journal Article J Cell Sci · January 1, 2016 The Abelson tyrosine kinases were initially identified as drivers of leukemia in mice and humans. The Abl family kinases Abl1 and Abl2 regulate diverse cellular processes during development and normal homeostasis, and their functions are subverted during i ... Full text Link to item Cite

The Emerging Role of ABL Kinases in Solid Tumors.

Journal Article Trends Cancer · October 1, 2015 The Abelson (ABL) tyrosine kinases were identified as drivers of leukemia in mice and humans. Emerging data has shown a role for the ABL family kinases, ABL1 and ABL2, in the progression of several solid tumors. This review will focus on recent reports of ... Full text Link to item Cite

ShcA regulates thymocyte proliferation through specific transcription factors and a c-Abl-dependent signaling axis.

Journal Article Mol Cell Biol · April 2015 Signaling via the pre-T-cell receptor (pre-TCR), along with associated signals from Notch and chemokine receptors, regulates the β-selection checkpoint that operates on CD4(-) CD8(-) doubly negative (DN) thymocytes. Since many hematopoietic malignancies ar ... Full text Link to item Cite

Abl Kinases Regulate HGF/Met Signaling Required for Epithelial Cell Scattering, Tubulogenesis and Motility.

Journal Article PLoS One · 2015 Tight regulation of receptor tyrosine kinases (RTKs) is crucial for normal development and homeostasis. Dysregulation of RTKs signaling is associated with diverse pathological conditions including cancer. The Met RTK is the receptor for hepatocyte growth f ... Full text Link to item Cite

Targeting ABL1-mediated oxidative stress adaptation in fumarate hydratase-deficient cancer.

Journal Article Cancer Cell · December 8, 2014 Patients with germline fumarate hydratase (FH) mutation are predisposed to develop aggressive kidney cancer with few treatment options and poor therapeutic outcomes. Activity of the proto-oncogene ABL1 is upregulated in FH-deficient kidney tumors and drive ... Full text Link to item Cite

Role of ABL family kinases in cancer: from leukaemia to solid tumours.

Journal Article Nat Rev Cancer · August 2013 The Abelson (ABL) family of nonreceptor tyrosine kinases, ABL1 and ABL2, transduces diverse extracellular signals to protein networks that control proliferation, survival, migration and invasion. ABL1 was first identified as an oncogene required for the de ... Full text Link to item Cite

Abl kinases are required for vascular function, Tie2 expression, and angiopoietin-1-mediated survival.

Journal Article Proc Natl Acad Sci U S A · July 23, 2013 Endothelial dysfunction is associated with diverse cardiovascular pathologies. Here, we show a previously unappreciated role for the Abelson (Abl) family kinases (Abl and Arg) in endothelial function and the regulation of angiogenic factor pathways importa ... Full text Link to item Cite

Abl family kinases regulate endothelial barrier function in vitro and in mice.

Journal Article PLoS One · 2013 The maintenance of endothelial barrier function is essential for normal physiology, and increased vascular permeability is a feature of a wide variety of pathological conditions, leading to complications including edema and tissue damage. Use of the pharma ... Full text Link to item Cite

Abl family kinases regulate FcγR-mediated phagocytosis in murine macrophages.

Journal Article J Immunol · December 1, 2012 Phagocytosis of Ab-coated pathogens is mediated through FcγRs, which activate intracellular signaling pathways to drive actin cytoskeletal rearrangements. Abl and Arg define a family of nonreceptor tyrosine kinases that regulate actin-dependent processes i ... Full text Link to item Cite

Abl family kinases modulate T cell-mediated inflammation and chemokine-induced migration through the adaptor HEF1 and the GTPase Rap1.

Journal Article Sci Signal · July 17, 2012 Chemokine signaling is critical for T cell function during homeostasis and inflammation and directs T cell polarity and migration through the activation of specific intracellular pathways. Here, we uncovered a previously uncharacterized role for the Abl fa ... Full text Link to item Cite

Arg kinase regulates epithelial cell polarity by targeting β1-integrin and small GTPase pathways.

Journal Article Curr Biol · September 27, 2011 BACKGROUND: Establishment and maintenance of epithelial cell polarity is regulated in part by signaling from adhesion receptors. Loss of cell polarity is associated with multiple pathologies including the initiation and progression of various cancers. The ... Full text Link to item Cite

Abl-interactor-1 (Abi1) has a role in cardiovascular and placental development and is a binding partner of the alpha4 integrin.

Journal Article Proc Natl Acad Sci U S A · January 4, 2011 Dynamic signals linking the actin cytoskeleton and cell adhesion receptors are essential for morphogenesis during development and normal tissue homeostasis. Abi1 is a central regulator of actin polymerization through interactions with multiple protein comp ... Full text Link to item Cite

Abl kinases are required for invadopodia formation and chemokine-induced invasion.

Journal Article J Biol Chem · December 17, 2010 The Abl tyrosine kinases, Abl and Arg, play a role in the regulation of the actin cytoskeleton by modulating cell-cell adhesion and cell motility. Deregulation of both the actin cytoskeleton and Abl kinases have been implicated in cancers. Abl kinase activ ... Full text Link to item Cite

Regulation of cell-cell adhesion by Abi/Diaphanous complexes.

Journal Article Mol Cell Biol · April 2009 Actin polymerization provides the driving force for the formation of cell-cell junctions and is mediated by two types of actin nucleators, Arp2/3 and formins. Proteins required for coordinately linking cadherin-mediated adhesion to Arp2/3-dependent versus ... Full text Link to item Cite

Abl tyrosine kinases in T-cell signaling.

Journal Article Immunol Rev · March 2009 Stimulation of the T-cell antigen receptor (TCR) leads to the activation of signaling pathways that are essential for T-cell development and the response of mature T cells to antigens. The TCR has no intrinsic catalytic activity, but TCR engagement results ... Full text Link to item Cite

Abl kinases regulate autophagy by promoting the trafficking and function of lysosomal components.

Journal Article J Biol Chem · December 19, 2008 Autophagy is a lysosome-dependent degradative pathway that regulates the turnover of intracellular organelles, parasites, and long-lived proteins. Deregulation of autophagy results in a variety of pathological conditions, but little is known regarding the ... Full text Link to item Cite

Targeting N-cadherin enhances antitumor activity of cytotoxic therapies in melanoma treatment.

Journal Article Cancer Res · May 15, 2008 Malignant transformation in melanoma is characterized by a phenotype "switch" from E- to N-cadherin, which is associated with increased motility and invasiveness of the tumor and altered signaling, leading to decreased apoptosis. We hypothesized that the n ... Full text Link to item Cite

Abl tyrosine kinases modulate cadherin-dependent adhesion upstream and downstream of Rho family GTPases.

Journal Article Cell Cycle · February 15, 2008 Formation and dissolution of intercellular adhesions are processes of paramount importance during tissue morphogenesis and for pathological conditions such as tumor metastasis. Cadherin-mediated intercellular adhesion requires dynamic regulation of the act ... Full text Link to item Cite

Phosphorylation of c-Abl by protein kinase Pak2 regulates differential binding of ABI2 and CRK.

Journal Article Biochemistry · January 22, 2008 The tyrosine kinase c-Abl is implicated in a variety of cellular processes that are tightly regulated by c-Abl kinase activity and/or by interactions between c-Abl and other signaling molecules. The interaction of c-Abl with the Abl interactor protein Abi2 ... Full text Link to item Cite

Defective T cell development and function in the absence of Abelson kinases.

Journal Article J Immunol · December 1, 2007 Featured Publication Thymocyte proliferation, survival, and differentiation are tightly controlled by signaling from the pre-TCR. In this study, we show for the first time that the Abelson (Abl) kinases regulate proximal signaling downstream of the pre-TCR. Conditional deletio ... Full text Link to item Cite

Abl tyrosine kinases regulate cell-cell adhesion through Rho GTPases.

Journal Article Proc Natl Acad Sci U S A · November 6, 2007 Featured Publication Adherens junctions are calcium-dependent cell-cell contacts that link neighboring cells through cadherin receptors. Coordinated regulation of the actin cytoskeleton by the Rho GTPases is required for the formation and dissolution of adherens junctions. How ... Full text Link to item Cite

Abi-1 forms an epidermal growth factor-inducible complex with Cbl: role in receptor endocytosis.

Journal Article Cell Signal · July 2007 Featured Publication The Abl-interactor (Abi) proteins are involved in the regulation of actin polymerization and have recently been shown to modulate epidermal growth factor receptor (EGFR) endocytosis. Here we describe the identification of a novel complex between Abi-1 and ... Full text Link to item Cite

Abl tyrosine kinase regulates endocytosis of the epidermal growth factor receptor.

Journal Article J Biol Chem · October 27, 2006 Featured Publication Signal attenuation from ligand-activated epidermal growth factor receptor (EGFR) is mediated in part by receptor endocytosis and trafficking to the lysosomal degradative compartment. Uncoupling the activated EGFR from endocytosis and degradation has emerge ... Full text Link to item Cite

The Caenorhabditis elegans ABL-1 tyrosine kinase is required for Shigella flexneri pathogenesis.

Journal Article Appl Environ Microbiol · July 2006 Shigellosis is a diarrheal disease caused by the gram-negative bacterium Shigella flexneri. Following ingestion of the bacterium, S. flexneri interferes with innate immunity, establishes an infection within the human colon, and initiates an inflammatory re ... Full text Link to item Cite

Role for the Abi/wave protein complex in T cell receptor-mediated proliferation and cytoskeletal remodeling.

Journal Article Curr Biol · January 10, 2006 Featured Publication BACKGROUND: The molecular reorganization of signaling molecules after T cell receptor (TCR) activation is accompanied by polymerization of actin at the site of contact between a T cell and an antigen-presenting cell (APC), as well as extension of actin-ric ... Full text Link to item Cite

Lower capillarization, VEGF protein, and VEGF mRNA response to acute exercise in the vastus lateralis muscle of aged vs. young women.

Journal Article J Appl Physiol (1985) · November 2005 In humans, the majority of studies demonstrate an age-associated reduction in the number of capillaries surrounding skeletal muscle fibers; however, recent reports in rats suggest that muscle capillarization is well maintained with advanced age. In sedenta ... Full text Link to item Cite

Abl kinases regulate actin comet tail elongation via an N-WASP-dependent pathway.

Journal Article Mol Cell Biol · October 2005 Featured Publication Microbial pathogens have evolved diverse strategies to modulate the host cell cytoskeleton to achieve a productive infection and have proven instrumental for unraveling the molecular machinery that regulates actin polymerization. Here we uncover a mechanis ... Full text Link to item Cite

Stress and death: breaking up the c-Abl/14-3-3 complex in apoptosis.

Journal Article Nat Cell Biol · March 2005 Featured Publication Full text Link to item Cite

ABI2-deficient mice exhibit defective cell migration, aberrant dendritic spine morphogenesis, and deficits in learning and memory.

Journal Article Mol Cell Biol · December 2004 Featured Publication The Abl-interactor (Abi) family of adaptor proteins has been linked to signaling pathways involving the Abl tyrosine kinases and the Rac GTPase. Abi proteins localize to sites of actin polymerization in protrusive membrane structures and regulate actin dyn ... Full text Link to item Cite

Requirement for Abl kinases in T cell receptor signaling.

Journal Article Curr Biol · July 27, 2004 Featured Publication BACKGROUND: The c-Abl and Arg proteins comprise a unique family of nonreceptor tyrosine kinases that have been implicated in the regulation of cell proliferation and survival, cytoskeletal reorganization, cell migration, and the response to oxidative stres ... Full text Link to item Cite

Abl interactor 1 (Abi-1) wave-binding and SNARE domains regulate its nucleocytoplasmic shuttling, lamellipodium localization, and wave-1 levels.

Journal Article Mol Cell Biol · June 2004 Featured Publication The Abl interactor 1 (Abi-1) protein has been implicated in the regulation of actin dynamics and localizes to the tips of lamellipodia and filopodia. Here, we show that Abi-1 binds the actin nucleator protein Wave-1 through an amino-terminal Wave-binding ( ... Full text Link to item Cite

Bidirectional signaling links the Abelson kinases to the platelet-derived growth factor receptor.

Journal Article Mol Cell Biol · March 2004 Featured Publication The c-Abl nonreceptor tyrosine kinase is activated by growth factor signals such as the platelet-derived growth factor (PDGF) and functions downstream of the PDGF-beta receptor (PDGFR) to mediate biological processes such as membrane ruffling, mitogenesis, ... Full text Link to item Cite

Elevated expression of a subset of interferon inducible genes in primary bone marrow cells expressing p185 Bcr-Abl versus p210 Bcr-Abl by DNA microarray analysis.

Journal Article Leuk Res · March 2004 p185 Bcr-Abl has a more aggressive biological/clinical leukemia phenotype than p210 Bcr-Abl. In this study, we examined differential gene expression using microarrays to determine if upregulation or downregulation of specific genes may explain the distinct ... Full text Link to item Cite

Abl tyrosine kinases are required for infection by Shigella flexneri.

Journal Article EMBO J · October 15, 2003 Featured Publication Infection by the opportunistic bacterial pathogen Shigella flexneri stimulates tyrosine phosphorylation of host cell proteins, but the kinases involved and their effects on the regulation of cell signaling pathways during bacterial entry remain largely und ... Full text Link to item Cite

Postsynaptic requirement for Abl kinases in assembly of the neuromuscular junction.

Journal Article Nat Neurosci · July 2003 Featured Publication Agrin signals through the muscle-specific receptor tyrosine kinase (MuSK) to cluster acetylcholine receptors (AChRs) on the postsynaptic membrane of the neuromuscular junction (NMJ). This stands as the prevailing model of synapse induction by a presynaptic ... Full text Link to item Cite

A new link between the c-Abl tyrosine kinase and phosphoinositide signalling through PLC-gamma1.

Journal Article Nat Cell Biol · April 2003 Featured Publication The c-Abl tyrosine (Tyr) kinase is activated after platelet-derived-growth factor receptor (PDGFR) stimulation in a manner that is partially dependent on Src kinase activity. However, the activity of Src kinases alone is not sufficient for activation of c- ... Full text Link to item Cite

Bcr-Abl variants: biological and clinical aspects.

Journal Article Leuk Res · August 2002 Bcr-Abl is an oncogene that arises from fusion of the Bcr gene with the c-Abl proto-oncogene. Three different Bcr-Abl variants can be formed, depending on the amount of Bcr gene included: p185, p210, and p230. The three variants are associated with distinc ... Full text Link to item Cite

Activated c-Abl is degraded by the ubiquitin-dependent proteasome pathway.

Journal Article Curr Biol · November 13, 2001 C-Abl is a nonreceptor tyrosine kinase that is tightly regulated in the cell. Genetic data derived from studies in flies and mice strongly support a role for Abl kinases in the regulation of the cytoskeleton (reviewed in [1,2]). C-Abl can be activated by s ... Full text Link to item Cite

The Abl interactor proteins localize to sites of actin polymerization at the tips of lamellipodia and filopodia.

Journal Article Curr Biol · June 5, 2001 Cell movement is mediated by the protrusion of cytoplasm in the form of sheet- and rod-like extensions, termed lamellipodia and filopodia. Protrusion is driven by actin polymerization, a process that is regulated by signaling complexes that are, as yet, po ... Full text Link to item Cite

Functional interaction between c-Abl and the p21-activated protein kinase gamma-PAK.

Journal Article Proc Natl Acad Sci U S A · December 19, 2000 A member of the p21-activated protein kinase (PAK) family, gamma-PAK has cytostatic properties and is activated by cellular stresses such as hyperosmolarity or DNA damage. We report herein that gamma-PAK is associated in vivo with the nonreceptor protein t ... Full text Link to item Cite

The c-Abl tyrosine kinase is regulated downstream of the B cell antigen receptor and interacts with CD19.

Journal Article J Immunol · December 15, 2000 c-Abl is a nonreceptor tyrosine kinase that we have recently linked to growth factor receptor signaling. The c-Abl kinase is ubiquitously expressed and localizes to the cytoplasm, plasma membrane, cytoskeleton, and nucleus. Thus, c-Abl may regulate signali ... Full text Link to item Cite

Localization and phosphorylation of Abl-interactor proteins, Abi-1 and Abi-2, in the developing nervous system.

Journal Article Mol Cell Neurosci · September 2000 Abl-interactor (Abi) proteins are targets of Abl-family nonreceptor tyrosine kinases and are required for Rac-dependent cytoskeletal reorganization in response to growth factor stimulation. We asked if the expression, phosphorylation, and cellular localiza ... Full text Link to item Cite

Analysis of the biologic properties of p230 Bcr-Abl reveals unique and overlapping properties with the oncogenic p185 and p210 Bcr-Abl tyrosine kinases.

Journal Article Blood · May 1, 2000 The reciprocal translocation between chromosomes 9 and 22 that fuses coding sequences of the Bcr and Abl genes is responsible for a remarkably diverse group of hematologic malignancies. A newly described 230-kd form of Bcr-Abl has been associated with an i ... Link to item Cite

The BCR/ABL oncogene alters the chemotactic response to stromal-derived factor-1alpha.

Journal Article Blood · December 15, 1999 The chemokine stromal-derived factor-1alpha (SDF-1alpha) is a chemoattractant for CD34(+) progenitor cells, in vitro and in vivo. The receptor for SDF-1alpha, CXCR-4, is a 7 transmembrane domain receptor, which is also a coreceptor for human immunodeficien ... Link to item Cite

c-Abl is activated by growth factors and Src family kinases and has a role in the cellular response to PDGF.

Journal Article Genes Dev · September 15, 1999 The c-Abl tyrosine kinase localizes to the cytoplasm and plasma membrane in addition to the nucleus. However, there is little information regarding a role for c-Abl in the cytoplasm/plasma membrane compartments. Here we report that a membrane pool of c-Abl ... Full text Link to item Cite

Efficient and rapid induction of a chronic myelogenous leukemia-like myeloproliferative disease in mice receiving P210 bcr/abl-transduced bone marrow.

Journal Article Blood · November 15, 1998 Expression of the 210-kD bcr/abl fusion oncoprotein can cause a chronic myelogenous leukemia (CML)-like disease in mice receiving bone marrow cells transduced by bcr/abl-encoding retroviruses. However, previous methods failed to yield this disease at a fre ... Link to item Cite

Oncogenic Abl and Src tyrosine kinases elicit the ubiquitin-dependent degradation of target proteins through a Ras-independent pathway.

Journal Article Genes Dev · May 15, 1998 Oncogenic forms of the Abl and Src tyrosine kinases trigger the destruction of the Abi proteins, a family of Abl-interacting proteins that antagonize the oncogenic potential of Abl after overexpression in fibroblasts. The destruction of the Abi proteins re ... Full text Link to item Cite

Protein tyrosine phosphatase 1B antagonizes signalling by oncoprotein tyrosine kinase p210 bcr-abl in vivo.

Journal Article Mol Cell Biol · May 1998 The p210 bcr-abl protein tyrosine kinase (PTK) appears to be directly responsible for the initial manifestations of chronic myelogenous leukemia (CML). In contrast to the extensive characterization of the PTK and its effects on cell function, relatively li ... Full text Link to item Cite

A requirement for NF-kappaB activation in Bcr-Abl-mediated transformation.

Journal Article Genes Dev · April 1, 1998 Bcr-Abl is a chimeric oncoprotein that is strongly implicated in acute lymphoblastic (ALL) and chronic myelogenous leukemias (CML). This deregulated tyrosine kinase selectively causes hematopoietic disorders resembling human leukemias in animal models and ... Full text Link to item Cite

Targets of the ABL tyrosine kinases in normal and transformed cells.

Conference BRITISH JOURNAL OF CANCER · January 1, 1998 Link to item Cite

The amphiphysin-like protein 1 (ALP1) interacts functionally with the cABL tyrosine kinase and may play a role in cytoskeletal regulation.

Journal Article Proc Natl Acad Sci U S A · November 11, 1997 cABL is a protooncogene, activated in a subset of human leukemias, whose protein product is a nonreceptor tyrosine kinase of unknown function. cABL has a complex structure that includes several domains and motifs found in proteins implicated in signal tran ... Full text Link to item Cite

The Bcr-Abl tyrosine kinase activates mitogenic signaling pathways and stimulates G1-to-S phase transition in hematopoietic cells.

Journal Article Oncogene · November 6, 1997 Bcr-Abl is a constitutively active tyrosine kinase that is expressed in Philadelphia chromosome (Ph1)-positive human leukemias. Bcr-Abl has been shown to inhibit apoptosis and cause anchorage independent growth. However, its ability to activate mitogenic s ... Full text Link to item Cite

The BCR-ABL tyrosine kinase inhibits apoptosis by activating a Ras-dependent signaling pathway.

Journal Article Oncogene · December 19, 1996 BCR-ABL is a deregulated tyrosine kinase that is expressed in Philadelphia chromosome (Ph1) positive human leukemias. When expressed in hematopoietic cells, BCR-ABL causes cytokine independent proliferation, induces tumorigenic growth and prevents apoptosi ... Link to item Cite

Functional association of CD7 with phosphatidylinositol 3-kinase: interaction via a YEDM motif.

Journal Article Int Immunol · August 1996 Human CD7 is a 40 kDa protein expressed on thymocytes, early T, B, NK and myeloid lineage cells in bone marrow, and on mature T and NK cells. Previous studies suggested human CD7 may be involved in T and NK cell activation and/or adhesion, and that CD7-med ... Full text Link to item Cite

Nuclear tyrosine kinases: from Abl to WEE1.

Journal Article Curr Opin Cell Biol · April 1996 The notion of a critical role for protein tyrosine kinases in the nucleus is supported by recent findings linking these proteins with components of the cell cycle and with the transcription machinery. Several of these tyrosine kinases localize to both nucl ... Full text Link to item Cite

Dominant-negative mutants of Grb2 induced reversal of the transformed phenotypes caused by the point mutation-activated rat HER-2/Neu.

Journal Article J Biol Chem · December 22, 1995 To clarify the role of the Shc-Grb2-Sos trimer in the oncogenic signaling of the point mutation-activated HER-2/neu receptor tyrosine kinase (named p185), we interfered with the protein-protein interactions in the Shc.Grb2.Sos complex by introducing Grb2 m ... Full text Link to item Cite

Mutant forms of growth factor-binding protein-2 reverse BCR-ABL-induced transformation.

Journal Article Proc Natl Acad Sci U S A · November 21, 1995 Growth factor-binding protein 2 (Grb2) is an adaptor protein that links tyrosine kinases to Ras. BCR-ABL is a tyrosine kinase oncoprotein that is implicated in the pathogenesis of Philadelphia chromosome (Ph1)-positive leukemias. Grb2 forms a complex with ... Full text Link to item Cite

Abi-2, a novel SH3-containing protein interacts with the c-Abl tyrosine kinase and modulates c-Abl transforming activity.

Journal Article Genes Dev · November 1, 1995 A protein has been identified that interacts specifically with both the Src homologous 3 (SH3) domain and carboxy-terminal sequences of the c-Abl tyrosine kinase. The cDNA encoding the Abl interactor protein (Abi-2), was isolated from a human lymphocyte li ... Full text Link to item Cite

Structural and signaling requirements for BCR-ABL-mediated transformation and inhibition of apoptosis.

Journal Article Mol Cell Biol · October 1995 BCR-ABL is a deregulated tyrosine kinase expressed in Philadelphia chromosome-positive human leukemias. Prolongation of hematopoietic cell survival by inhibition of apoptosis has been proposed to be an integral component of BCR-ABL-induced chronic myelogen ... Full text Link to item Cite

Association of the protein kinases c-Bcr and Bcr-Abl with proteins of the 14-3-3 family.

Journal Article Science · October 7, 1994 In this study, a protein that interacts with sequences encoded by the first exon of the protein kinase Bcr was cloned. The Bcr-associated protein 1 (Bap-1) is a member of the 14-3-3 family of proteins. Bap-1 interacts with full-length c-Bcr and with the ch ... Full text Link to item Cite

BCR-ABL-induced oncogenesis is mediated by direct interaction with the SH2 domain of the GRB-2 adaptor protein.

Journal Article Cell · October 8, 1993 BCR-ABL is a chimeric oncoprotein that exhibits deregulated tyrosine kinase activity and is implicated in the pathogenesis of Philadelphia chromosome (Ph1)-positive human leukemias. Sequences within the first exon of BCR are required to activate the transf ... Link to item Cite

Oncogenic activation of c-ABL by mutation within its last exon.

Journal Article Mol Cell Biol · August 1993 The c-ABL proto-oncogene is a predominantly nuclear localized tyrosine kinase. A random mutagenesis scheme was used to isolate c-ABL mutants whose expression produced a transformed phenotype in rodent fibroblast cells. An in-frame deletion within the centr ... Full text Link to item Cite

En bloc substitution of the Src homology region 2 domain activates the transforming potential of the c-Abl protein tyrosine kinase.

Journal Article Proc Natl Acad Sci U S A · April 15, 1993 Src homology region 2 (SH2) domains are present in many proteins involved in signal transduction. In nonreceptor protein tyrosine kinases the SH2 domain has been implicated in regulation of tyrosine kinase activity and in mediating interactions involved in ... Full text Link to item Cite

SH1 domain autophosphorylation of P210 BCR/ABL is required for transformation but not growth factor independence.

Journal Article Mol Cell Biol · March 1993 P210 BCR/ABL is a chimeric oncogene implicated in the pathogenesis of chronic myelogenous leukemia. BCR sequences have been shown to be required for activation of the tyrosine kinase and transforming functions of BCR/ABL. In this work, we show that two oth ... Full text Link to item Cite

A limited set of SH2 domains binds BCR through a high-affinity phosphotyrosine-independent interaction.

Journal Article Mol Cell Biol · November 1992 SH2 (src homology region 2) domains are implicated in protein-protein interactions involved in signal transduction pathways. Isolated SH2 domains bind proteins that are tyrosine phosphorylated. A novel, phosphotyrosine-independent binding interaction betwe ... Full text Link to item Cite

The 5' non-coding region of the BCR/ABL oncogene augments its ability to stimulate the growth of immature lymphoid cells.

Journal Article Oncogene · August 1991 The Philadelphia chromosome (Ph1, t9:22;34:q11) is a reciprocal translocation between chromosome 22 and chromosome 9 which results in the formation of the chimeric BCR/ABL oncogene. Alternative forms of BCR/ABL are produced by splicing different sets of ex ... Link to item Cite

BCR sequences essential for transformation by the BCR-ABL oncogene bind to the ABL SH2 regulatory domain in a non-phosphotyrosine-dependent manner.

Journal Article Cell · July 12, 1991 BCR-ABL is a chimeric oncogene implicated in the pathogenesis of Philadelphia chromosome-positive human leukemias. BCR first exon sequences specifically activate the tyrosine kinase and transforming potential of BCR-ABL. We have tested the hypothesis that ... Full text Link to item Cite

Evidence for regulation of the human ABL tyrosine kinase by a cellular inhibitor.

Journal Article Proc Natl Acad Sci U S A · July 1, 1991 Phosphotyrosine cannot be detected on normal human ABL protein-tyrosine kinases, but activated oncogenic forms of the human ABL protein are phosphorylated on tyrosine in vivo. Activation of ABL can occur by substitution of the ABL first exon with breakpoin ... Full text Link to item Cite

BCR first exon sequences specifically activate the BCR/ABL tyrosine kinase oncogene of Philadelphia chromosome-positive human leukemias.

Journal Article Mol Cell Biol · April 1991 The c-abl proto-oncogene encodes a cytoplasmic tyrosine kinase which is homologous to the src gene product in its kinase domain and in the upstream kinase regulatory domains SH2 (src homology region 2) and SH3 (src homology region 3). The murine v-abl onco ... Full text Link to item Cite

Tyrosine kinase activity and transformation potency of bcr-abl oncogene products.

Journal Article Science · March 2, 1990 Oncogenic activation of the proto-oncogene c-abl in human leukemias occurs as a result of the addition of exons from the gene bcr and truncation of the first abl exon. Analysis of tyrosine kinase activity and quantitative measurement of transformation pote ... Full text Link to item Cite

P150c-abl is detected in mouse male germ cells by an in vitro kinase assay and is associated with stage-specific phosphoproteins in haploid cells.

Journal Article Oncogene · June 1989 We have utilized c-abl antibodies and an in vitro kinase assay to identify the protein products of the c-abl gene in mouse testis. Although the testis contains high levels of a unique c-abl mRNA, along with lower amounts of two c-abl mRNAs common to somati ... Link to item Cite

Baculovirus expression of functional P210 BCR-ABL oncogene product.

Journal Article Oncogene · June 1989 The chronic myelogenous leukemia-associated P210 BCR-ABL oncogene protein product has been produced using the baculovirus expression system. High-level expression of the P210 BCR-ABL protein required the removal of GC rich 5' non-coding sequences. P210 BCR ... Link to item Cite

Expression of a distinctive BCR-ABL oncogene in Ph1-positive acute lymphocytic leukemia (ALL).

Journal Article Science · February 12, 1988 The Philadelphia chromosome (Ph1) is a translocation between chromosomes 9 and 22 that is found in chronic myelogenous leukemia (CML) and a subset of acute lymphocytic leukemia patients (ALL). In CML, this results in the expression of a chimeric 8.5-kiloba ... Full text Link to item Cite

Role of the ABL oncogene tyrosine kinase activity in human leukaemia.

Journal Article Baillieres Clin Haematol · December 1987 A great deal of information has emerged over the past decade regarding the gene structures and corresponding protein products of the cellular and transformation-associated forms of the ABL tyrosine kinase family. Many reports have also detailed the biologi ... Full text Link to item Cite

Normal cellular and transformation-associated abl proteins share common sites for protein kinase C phosphorylation.

Journal Article Mol Cell Biol · December 1987 Viral transduction and chromosomal translocations of the c-abl gene result in the synthesis of abl proteins with structurally altered amino termini. These altered forms of the abl protein, but not the c-abl proteins, are detectably phosphorylated on tyrosi ... Full text Link to item Cite

Regulation of phosphorylation of aminoacyl-tRNA synthetases in the high molecular weight core complex in reticulocytes.

Journal Article J Biol Chem · May 5, 1987 Five aminoacyl-tRNA synthetases found in the high molecular weight core complex were phosphorylated in rabbit reticulocytes following labeling with 32P. The synthetases were isolated by affinity chromatography on tRNA-Sepharose followed by immunoprecipitat ... Link to item Cite

Identification of three protein kinases which phosphorylate threonyl-tRNA synthetase from rat liver.

Journal Article FEBS Lett · October 6, 1986 Threonyl-tRNA synthetase is phosphorylated in Chinese hamster ovary cells labeled with 32Pi [(1984) J. Biol. Chem. 259, 11160-11161]. Phosphorylation of the purified synthetase from rat liver has been examined with five different protein kinases. Three of ... Full text Link to item Cite

Alteration of aminoacyl-tRNA synthetase activities by phosphorylation with casein kinase I.

Journal Article J Biol Chem · September 25, 1985 The phosphorylation of a highly purified aminoacyl-tRNA synthetase complex from rabbit reticulocytes by the cyclic nucleotide-independent protein kinase, casein kinase I, has been examined, and the effects of phosphorylation on the synthetase activities we ... Link to item Cite