Expression and function of IA-2 family proteins, unique neuroendocrine-specific protein-tyrosine phosphatases.
IA-2 (also known as islet cell antigen ICA-512) and IA-2 beta (also known as phogrin, phosphatase homologue in granules of insulinoma) are major autoantigens in insulin-dependent diabetes mellitus (IDDM). Autoantibodies against both proteins are expressed years before clinical onset, and they become predictive markers for high-risk subjects. However, the role of these genes in the IDDM pathogenesis has been reported fairly negative by recent studies. IA-2 and IA-2 beta are type I transmembrane proteins that possess one inactive protein-tyrosine phosphatase (PTP) domain in the cytoplasmic region, and act as one of the constituents of regulated secretory pathways in various neuroendocrine cell types including pancreatic beta-cells. Existence of IA-2 homologues in different species suggests a fundamental role in neuroendocrine function. Studies of knockout animals have shown their involvement in maintaining hormone content, however, their specific steps in the secretory pathway IA-2 functions as well as their molecular mechanisms in the hormone content regulation are still unknown. More recent studies have suggested a novel function showing that they contribute to pancreatic beta-cell growth. This review attempts to show the possible biological functions of IA-2 family, focusing on their expression and localization in the neuroendocrine cells.
Torii
Seiji
S
Department of Molecular Medicine, Institute for Molecular and Cellular Regulation, Gunma University, Maebashi, Japan. storii@showa.gunma-u.ac.jp
D000818:Animals; D001324:Autoantigens / Q000235:genetics; D003922:Diabetes Mellitus, Type 1 / Q000235:genetics; D006801:Humans; D007328:Insulin / Q000502:physiology; D050417:Insulin-Secreting Cells / Q000187:drug effects / Q000502:physiology; D055099:Neuroendocrine Cells / Q000201:enzymology*; D054635:Receptor-Like Protein Tyrosine Phosphatases, Class 8 / Q000235:genetics / Q000502:physiology*; D022142:Secretory Vesicles / Q000201:enzymology; D015398:Signal Transduction / Q000502:physiology
D001324:Autoantigens; D007328:Insulin; C516863:Ptprn protein, mouse; D054635:Receptor-Like Protein Tyrosine Phosphatases, Class 8