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Expression and function of IA-2 family proteins, unique neuroendocrine-specific protein-tyrosine phosphatases Torii SEndocr J 2009[]; 56 (5): 639-48IA-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.|Animals[MESH]|Autoantigens/genetics[MESH]|Diabetes Mellitus, Type 1/genetics[MESH]|Humans[MESH]|Insulin-Secreting Cells/drug effects/physiology[MESH]|Insulin/physiology[MESH]|Neuroendocrine Cells/*enzymology[MESH]|Receptor-Like Protein Tyrosine Phosphatases, Class 8/genetics/*physiology[MESH]|Secretory Vesicles/enzymology[MESH]|Signal Transduction/physiology[MESH] |
