Receptor • cell signaling • endosomes • tyrosine kinase • phosphotyrosine phosphatase
My group has studied peptide hormone receptor distribution in tissues, including in the central nervous system (CNS). We have also focused on the mechanisms of cell signaling by insulin and growth factors, especially the insulin-like growth factors and epidermal growth factor (EGF). In our effort to understand physiology and resultant pathology, we have emphasized the study of cell signaling in normal tissues—both in cultured cells (hepatocytes) and in vivo (intact liver). We believed this approach was essential in order to define physiological pathways that are otherwise altered in diseased cells. Of note was our discovery of the role of internalization of ligand-receptor complexes into endosomes (ENs), the delineation of a key role for phosphotyrosine phosphatases in regulating receptor tyrosine kinase function (notably that of the insulin receptor kinase) within ENs, and the identification of new molecules in the pathway of insulin and EGF signaling, including IRS3, Gab2, and SHPTP1.
Posner, B.I. Insulin Signaling – The Inside Story. Can.Journal of Diabetes 41: 108-114, 201. doi: 10.1016/j.jcjd.2016.07.002. PMID: 27614806.
Posner, B.I., R. Faure, J.W. Burgess, A.P. Bevan, D. Lachance, G. Zhang-Sun, I.G. Fantus, J.B. Ng, D.A. Hall, B. Soo Lum, and A. Shaver. Peroxovanadium Compounds: A new class of potent phosphotyrosine phosphatase inhibitors which are insulin mimetic. J. Biol. Chem. 269: 4596-4604, 1994. PMID: 8308031.
Shen, S.H., L. Bastien, B.I. Posner and P. Chretien. A protein tyrosine phosphatase with sequence similarity to the SH2 domain of the protein tyrosine kinases. Nature 352: 736-739, 1991. DOI: 10.1038/352736a0. PMID: 1652101.
Tannenbaum, G.S., H.J. Guyda and B.I. Posner. Insulin-like growth factors: A role in growth hormone negative feedback and body weight regulation via the brain. Science 220: 77-79, 1983. DOI: 10.1126/science.6338593. PMID: 6338593.
Van Houten, M., B.I. Posner, B.M. Kopriwa and J.R. Brawer. Insulin binding sites localized to nerve terminals in rat median eminence and arcuate nucleus. Science 207: 1081-1083, 1980. DOI: 10.1126/science.6986652. PMID: 6986652.