Overview
1. Biology of α2MSR: Ligands binding and their regulation, receptor upregulation, defining signaling cascades components, modulation of ser/thr/tyr kinase activities, cellular responses (mitogenesis, gene expression), physiological relevance.
2. Receptor activation, and membrane phospholipases - PLA2, PI-PLCb, PI-PLCg, PC-PLC, PLD, sphingomyelinase, and ceramide signaling, regulation, role in mitogenesis.
3. α2MSR and malignancy - Prostate cancer cell line e.g. 1LN, PC3, LnCap as model. Modulation of cellular responses by inhibitors of down stream signaling cascades, a2MSR and p53 (tumor suppressor gene) expression.
4. Cations, α2MSR and genotoxicity - bivalen and trivalen cations and binding of α2M* to α2MSR, signaling cascades components and their regulation, mitogenesis.
5. Isolation, purification and characterization of α - Autophosphorylation of the receptor on ligands binding, amino acid residues involved in receptor activation, mechanism of receptor desensitization, modulators/coactivators binding domains on the receptor, differences between LRP/α2MR and α2MSR, transfection studies.
6. α2MSR and neuronal development -
7. Internalization and proteosomies targeting of alpha-2-macroglobulin signaling receptor- A possible metabolic advantage for the isolation of α2MSR during its proteosome targeting.
8. Cadmium and development of prostate malignancy-use of human prostate cancer cell liens as model. Delineating the role of farnesyl transferase, p21-Ras activation, MAPK and PI 3-kinase signaling cascades, transcription factors and early response genes in malignancy development.
2. Receptor activation, and membrane phospholipases - PLA2, PI-PLCb, PI-PLCg, PC-PLC, PLD, sphingomyelinase, and ceramide signaling, regulation, role in mitogenesis.
3. α2MSR and malignancy - Prostate cancer cell line e.g. 1LN, PC3, LnCap as model. Modulation of cellular responses by inhibitors of down stream signaling cascades, a2MSR and p53 (tumor suppressor gene) expression.
4. Cations, α2MSR and genotoxicity - bivalen and trivalen cations and binding of α2M* to α2MSR, signaling cascades components and their regulation, mitogenesis.
5. Isolation, purification and characterization of α - Autophosphorylation of the receptor on ligands binding, amino acid residues involved in receptor activation, mechanism of receptor desensitization, modulators/coactivators binding domains on the receptor, differences between LRP/α2MR and α2MSR, transfection studies.
6. α2MSR and neuronal development -
7. Internalization and proteosomies targeting of alpha-2-macroglobulin signaling receptor- A possible metabolic advantage for the isolation of α2MSR during its proteosome targeting.
8. Cadmium and development of prostate malignancy-use of human prostate cancer cell liens as model. Delineating the role of farnesyl transferase, p21-Ras activation, MAPK and PI 3-kinase signaling cascades, transcription factors and early response genes in malignancy development.
Current Appointments & Affiliations
Professor Emeritus of Pathology
·
2014 - Present
Pathology,
Clinical Science Departments
Recent Publications
Activated α2-macroglobulin binding to human prostate cancer cells triggers insulin-like responses.
Journal Article J Biol Chem · April 10, 2015 Ligation of cell surface GRP78 by activated α2-macroglobulin (α2M*) promotes cell proliferation and suppresses apoptosis. α2M*-treated human prostate cancer cells exhibit a 2-3-fold increase in glucose uptake and lactate secretion, an effect similar to ins ... Full text Link to item CiteActivated α2-macroglobulin binding to cell surface GRP78 induces T-loop phosphorylation of Akt1 by PDK1 in association with Raptor.
Journal Article PLoS One · 2014 PDK1 phosphorylates multiple substrates including Akt by PIP3-dependent mechanisms. In this report we provide evidence that in prostate cancer cells stimulated with activated α2-macroglobulin (α2M*) PDK1 phosphorylates Akt in the T-loop at Thr(308) by usin ... Full text Link to item CiteThe monomeric receptor binding domain of tetrameric α2-macroglobulin binds to cell surface GRP78 triggering equivalent activation of signaling cascades.
Journal Article Biochemistry · June 11, 2013 α2-Macroglobulin (α2M) is a broad spectrum proteinase inhibitor that when activated by proteinases (α2M*) undergoes a major conformational change exposing receptor recognition sites in each of its four subunits. These complexes bind to two distinct recepto ... Full text Link to item CiteRecent Grants
Cell Receptors In Coagulation And Atherogenesis
ResearchCo Investigator · Awarded by National Institutes of Health · 1979 - 2008View All Grants
Education, Training & Certifications
Kansas State University ·
1959
Ph.D.