Barry Posner, MD, FRSC, FRCPC, FACP
diabetes mellitus • endocytosis • growth factor action • insulin action • intracellular signaling
My research has focused on the study of insulin and growth factor (GF) action emphasizing their relationship to the pathogenesis of type 2 diabetes mellitus. Both insulin and GFs bind to cell surface receptors followed by activation and internalization of these receptors into intracellular organelles, known as endosomes. Substrates of both the insulin receptor (IR) and GF receptors have been demonstrated within endosomes. We identified the peroxovanadium (pV) compounds as potent insulin mimickers acting through the inhibition of endosomal enzymes deactivating the IR. Thus the pV compounds, by promoting insulin signaling, could evoke hypoglycemia in normal and diabetic rats. This led to studies defining various endosomal processes which regulate IR and GF receptor functions. Of interest has been the question of how GF and IR signaling, though involving similar biochemical pathways , nevertheless produce responses specific to each agent. Recent work has sought to address both genetic and epigenetic bases of Type 2 Diabetes Mellitus.
Balbis, A. and B.I.Posner. Compartmentalization of EGFR in Cellular Membranes: Role of Membrane Rafts. J.Cell Biochemistry 109: 1103-1108, 2010.
Posner, B.I. and S.Laporte. Cellular Signaling of Peptide Hormones and Growth Factors. Prog Brain Res. 181:1-16, 2010.
M. Fedjaev, Y. Xu, K. Vetrogon, M.R. DiFalco, M. Ashmarina, I. Nifant'ev, B. I. Posner and A.V. Pshezhetsky. Global Analysis of Protein Phosphorylation Networks in Insulin Signaling by Sequential Enrichment of Phosphoproteins and Phosphopeptides. Molecular Biosystems 8 :1461-71, 2012.
Xu, Y., A.Parmar, A.Balbis, E.Roux, S.Chevalier, V.Dumas, and B.I.Posner. EGF-induced Vacuolar ATPase Assembly: A Role in Signaling via mTORC1 Activation. J.Biol.Chem. 287(July 27): 26409–26422, 2012.
Posner, B.I. and J.J.M.Bergeron. Assessment of Internalization and Endosomal Signaling: Studies with Insulin and EGF. Methods in Enzymology (in press).