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Gene Review

Ptprn2  -  protein tyrosine phosphatase, receptor...

Mus musculus

Synonyms: 4930425H11Rik, IA-2 beta, IA-2beta, IA2beta, PTP IA-2beta, ...
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Disease relevance of Ptprn2


High impact information on Ptprn2

  • These findings strongly suggest that inhibitory effects of ghrelin on glucose-stimulated insulin secretion are at least partly due to increased expression of IA-2beta induced by ghrelin [2].
  • A partial sequence of the extracellular domain of IA-2beta indicates that it differs substantially (only 26% identical) from that of IA-2 [1].
  • PTP-NP, a new member of the receptor protein tyrosine phosphatase family, implicated in development of nervous system and pancreatic endocrine cells [4].
  • At early organogenesis, in situ hybridization with a probe for the PTP-NP extracellular region detects expression confined to the region of the developing pancreas, an organ of medical importance, but poorly understood with regard to molecular mechanisms of developmental control [4].
  • To search for a ligand of PTP-NP, a fusion protein probe was made with the extracellular domain fused to an alkaline phosphatase tag [4].

Biological context of Ptprn2

  • Spreading of antibody responses to GAD or IA-2/IA-2beta following immunization was rare, and antibody epitope spreading was only detected in IA-2beta immunized mice [5].
  • Phosphorylation of the phogrin cytosolic domain by beta-cell homogenates was Ca(2+)-independent but stimulated by cAMP [6].
  • To monitor the motion of insulin secretory granules throughout exocytosis/endocytosis, pHluorin was inserted between the third and fourth amino acids after the identified signal-peptide cleavage site of rat phogrin cDNA [7].
  • Thus our observations are consistent with a role for phogrin phosphorylation in the signal-transduction pathway at a site proximal to the exocytic event itself, possibly regulating secretory-granule mobilization and recruitment to the exocytic site [8].
  • We have examined the recycling of endogenous phogrin following exocytosis in insulin secreting Min6 beta-cells by monitoring stimulus dependent-uptake of antibodies directed against the lumenal domain of the protein [9].

Anatomical context of Ptprn2

  • Taken together, our experiments show that the dense core vesicle proteins IA-2 and IA-2beta, alone or in combination, are involved in insulin secretion, but neither alone nor in combination are they required for the development of diabetes in NOD mice [10].
  • IA-2 and IA-2beta are members of the transmembrane protein tyrosine phosphatase family located in dense core vesicles of neuroendocrine cells, including the beta-cells of pancreatic islets [10].
  • Eight phogrin-specific T-cell clones were generated from NOD mice, and their epitopes were mapped [11].
  • Phogrin, a 60/64-kDa integral membrane protein of dense-core granules in neuroendocrine cells, is phosphorylated in a Ca(2+)-sensitive manner in response to secretagogue stimulation of pancreatic beta-cells [6].
  • Phogrin is exposed on the cell surface in response to stimuli and progressively internalized to a perinuclear compartment that overlaps with recycling endosomes marked by transferrin [12].

Associations of Ptprn2 with chemical compounds

  • In the present study, by mating C57BL/6Nci IA-2(+/-) with IA-2beta(+/-) mice, we generated double knockout mice (IA-2(-/-)/IA-2beta(-/-)) to study the effect of the combined deletion of these two proteins on insulin secretion and blood glucose levels [10].
  • Full-length wild-type phogrin, as well as mutant versions where Ser-680 and Thr-699 had been replaced either by alanines or by aspartic acid residues, were targeted to secretory granules in transfected AtT20 neuroendocrine cells [6].
  • Subfractionation of the insulin granule components by hypotonic lysis followed by sucrose gradient centrifugation showed that glucokinase colocalized with the granule membrane marker phogrin and not with insulin [13].
  • In MIN6 beta-cells, the PKA inhibitor H-89 prevented Ca(2+)-dependent phogrin phosphorylation in response to glucose, suggesting that Ca(2+) exerts its effect on phogrin phosphorylation through regulating the activity of PKA [6].
  • Previous studies with phogrin (IA-2beta) identified sorting signals in the luminal domain that is cleaved post-translationally; we now describe an independent DCV targeting motif in the cytosolic domain that may function at the level of endocytosis and recycling [12].

Other interactions of Ptprn2


Analytical, diagnostic and therapeutic context of Ptprn2


  1. Identification of a second transmembrane protein tyrosine phosphatase, IA-2beta, as an autoantigen in insulin-dependent diabetes mellitus: precursor of the 37-kDa tryptic fragment. Lu, J., Li, Q., Xie, H., Chen, Z.J., Borovitskaya, A.E., Maclaren, N.K., Notkins, A.L., Lan, M.S. Proc. Natl. Acad. Sci. U.S.A. (1996) [Pubmed]
  2. IA-2beta, but not IA-2, is induced by ghrelin and inhibits glucose-stimulated insulin secretion. Doi, A., Shono, T., Nishi, M., Furuta, H., Sasaki, H., Nanjo, K. Proc. Natl. Acad. Sci. U.S.A. (2006) [Pubmed]
  3. Disruption of the transmembrane dense core vesicle proteins IA-2 and IA-2beta causes female infertility. Kubosaki, A., Nakamura, S., Clark, A., Morris, J.F., Notkins, A.L. Endocrinology (2006) [Pubmed]
  4. PTP-NP, a new member of the receptor protein tyrosine phosphatase family, implicated in development of nervous system and pancreatic endocrine cells. Chiang, M.K., Flanagan, J.G. Development (1996) [Pubmed]
  5. Characterization of antibody responses to endogenous and exogenous antigen in the nonobese diabetic mouse. Koczwara, K., Schenker, M., Schmid, S., Kredel, K., Ziegler, A.G., Bonifacio, E. Clin. Immunol. (2003) [Pubmed]
  6. Secretagogue-dependent phosphorylation of the insulin granule membrane protein phogrin is mediated by cAMP-dependent protein kinase. Wasmeier, C., Hutton, J.C. J. Biol. Chem. (2001) [Pubmed]
  7. Monitoring of exocytosis and endocytosis of insulin secretory granules in the pancreatic beta-cell line MIN6 using pH-sensitive green fluorescent protein (pHluorin) and confocal laser microscopy. Ohara-Imaizumi, M., Nakamichi, Y., Tanaka, T., Katsuta, H., Ishida, H., Nagamatsu, S. Biochem. J. (2002) [Pubmed]
  8. Secretagogue-dependent phosphorylation of phogrin, an insulin granule membrane protein tyrosine phosphatase homologue. Wasmeier, C., Hutton, J.C. Biochem. J. (1999) [Pubmed]
  9. Recycling of the dense-core vesicle membrane protein phogrin in Min6 beta-cells. Vo, Y.P., Hutton, J.C., Angleson, J.K. Biochem. Biophys. Res. Commun. (2004) [Pubmed]
  10. Dense Core Vesicle Proteins IA-2 and IA-2{beta}: Metabolic Alterations in Double Knockout Mice. Kubosaki, A., Nakamura, S., Notkins, A.L. Diabetes (2005) [Pubmed]
  11. T-cell epitope analysis on the autoantigen phogrin (IA-2beta) in the nonobese diabetic mouse. Kelemen, K., Wegmann, D.R., Hutton, J.C. Diabetes (2001) [Pubmed]
  12. An extended tyrosine-targeting motif for endocytosis and recycling of the dense-core vesicle membrane protein phogrin. Wasmeier, C., Burgos, P.V., Trudeau, T., Davidson, H.W., Hutton, J.C. Traffic (2005) [Pubmed]
  13. Glucokinase is an integral component of the insulin granules in glucose-responsive insulin secretory cells and does not translocate during glucose stimulation. Arden, C., Harbottle, A., Baltrusch, S., Tiedge, M., Agius, L. Diabetes (2004) [Pubmed]
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