Expression and function of IA-2 family proteins, unique neuroendocrine-specific protein-tyrosine phosphatases

Endocr J. 2009;56(5):639-48. doi: 10.1507/endocrj.k09e-157. Epub 2009 Jun 24.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Autoantigens / genetics
  • Diabetes Mellitus, Type 1 / genetics
  • Humans
  • Insulin / physiology
  • Insulin-Secreting Cells / drug effects
  • Insulin-Secreting Cells / physiology
  • Neuroendocrine Cells / enzymology*
  • Receptor-Like Protein Tyrosine Phosphatases, Class 8 / genetics
  • Receptor-Like Protein Tyrosine Phosphatases, Class 8 / physiology*
  • Secretory Vesicles / enzymology
  • Signal Transduction / physiology

Substances

  • Autoantigens
  • Insulin
  • Ptprn protein, mouse
  • Receptor-Like Protein Tyrosine Phosphatases, Class 8