The world's first wiki where authorship really matters (Nature Genetics, 2008). Due credit and reputation for authors. Imagine a global collaborative knowledge base for original thoughts. Search thousands of articles and collaborate with scientists around the globe.

wikigene or wiki gene protein drug chemical gene disease author authorship tracking collaborative publishing evolutionary knowledge reputation system wiki2.0 global collaboration genes proteins drugs chemicals diseases compound
Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)
 

Links

 

Gene Review

Ptprn2  -  protein tyrosine phosphatase, receptor...

Mus musculus

Synonyms: 4930425H11Rik, IA-2 beta, IA-2beta, IA2beta, PTP IA-2beta, ...
 
 
Welcome! If you are familiar with the subject of this article, you can contribute to this open access knowledge base by deleting incorrect information, restructuring or completely rewriting any text. Read more.
 

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

References

  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]
 
WikiGenes - Universities