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Reg1  -  regenerating islet-derived 1

Mus musculus

Synonyms: Islet of Langerhans regenerating protein 1, Lithostathine-1, PSP, PTP, Pancreatic stone protein 1, ...
 
 
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Disease relevance of Reg1

  • The effect of IFNbeta on Reg1 and Reg2 expression was assessed in the NOD insulinoma cell line NIT-1 [1].
  • We examined the effect of Listeria monocytogenes infection of J774 macrophage-like mouse cells on induction of several stress genes, including genes for heat shock proteins (HSPs) and a protein-tyrosine phosphatase (PTP), to understand the host response in various steps of the bacterial invasion process [2].
  • The PTP inhibitors ALN, orthovanadate, and PAO suppressed in vitro formation of multinucleated osteoclasts from osteoclast precursors and in vitro bone resorption by isolated rat osteoclasts (pit formation) with estimated IC50 values of 10 microM, 3 microM, and 0.05 microM, respectively [3].
  • This modulation of myocytes by hypoxia was suggested further by the induction of 100-kDa and 9-kDa proteins (PSP 100 and PSP 9) which were otherwise only detectable in myoblasts [4].
  • The Yersinia protein tyrosine phosphatase (PTP) YopH is translocated into eukaryotic cells by a type III secretion system that requires bacterial-host cell contact [5].
 

Psychiatry related information on Reg1

  • In all, PTP epsilon antagonizes activation of Kv channels by tyrosine kinases in vivo, and affects Schwann cell function during a critical period of Schwann cell growth and myelination [6].
  • Reactive microglia have been suggested to play a role in the Alzheimer's disease (AD) process, and previous studies have shown that expression of CD45, a membrane-bound protein-tyrosine phosphatase (PTP), is elevated in microglia in AD brain compared with controls [7].
 

High impact information on Reg1

  • We have discovered that a member of the dual-specific protein tyrosine phosphatase (DS-PTP) family, PTPMT1 (PTP localized to the Mitochondrion 1) resides nearly exclusively in mitochondria [8].
  • In addition to giving novel insights into the mechanisms involved in the negative regulation of T-cell activation, these findings indicate that the association of an inhibitory PTK with a PTP constitutes a more efficient means of inhibiting signal transduction by Src family kinases in vivo [9].
  • Subsequent studies uncovered that, via its SH3 domain, p50(csk) was associated with PEP, a proline-enriched protein tyrosine phosphatase (PTP) of unknown function expressed in hemopoietic cells [9].
  • The cytosolic SHP-1 and transmembrane CD45 protein tyrosine phosphatases (PTP) play critical roles in regulating signal transduction via the B cell antigen receptor (BCR) [10].
  • We investigated the molecular and cellular actions of receptor protein tyrosine phosphatase (PTP) alpha in integrin signaling using immortalized fibroblasts derived from wild-type and PTP alpha-deficient mouse embryos [11].
 

Chemical compound and disease context of Reg1

  • In the present study, the significance of protein tyrosine phosphatases (PTP) and ser/thr protein phosphatases (PP) in alpha4beta1 and alpha5beta1 integrin-mediated mouse melanoma B16F1 cell anchorage and migration on fibronectin was characterized using phosphatase inhibitors [12].
 

Biological context of Reg1

  • PTP epsilon-cytoplasmic is therefore the initial example to our knowledge of a nontransmembranal protein-tyrosine phosphatase that contains two tandem of catalytic domains [13].
  • Mutations in other virulence genes did not affect transcription of PTP or HSP90 [2].
  • These results suggest that phagocytosis of L. monocytogenes triggers transcription of HSP70 mRNA in macrophages; however, escape from the phagosome appears to be necessary for induction of PTP and HSP90 mRNA [2].
  • We conclude that physiological signals can regulate dimerization and phosphorylation of cyt-PTP epsilon in the absence of direct interaction between the PTP and extracellular molecules [14].
  • Furthermore, dimerization can be mediated by the D2 domain and does not strictly require the presence of PTP extracellular domains [14].
 

Anatomical context of Reg1

  • Previously, other Reg proteins (Reg1 and islet neogenesis-associated protein) have been shown to promote islet cell replication and neogenesis [15].
  • REG1 and REG2 proteins, which may be involved in the proliferation of pancreatic beta cells, were up-regulated very early in the progression of obese mice to T2DM [16].
  • We report that mice lacking PTP epsilon exhibit hypomyelination of sciatic nerve axons at an early post-natal age [6].
  • A listeriolysin-negative mutant of L. monocytogenes strain EGD and a noninvasive species of Listeria, Listeria innocua, did not induce PTP or HSP90 mRNA in infected macrophages [2].
  • Since both PTP and HSP90 may have links with signal transduction pathways in eukaryotic cells, the induction of these mRNAs suggests a role for L. monocytogenes in influencing the signal transduction routes of the host cell [2].
 

Associations of Reg1 with chemical compounds

  • Protein tyrosine phosphatase (PTP) 1B has been implicated as a negative regulator of multiple signaling pathways downstream of receptor tyrosine kinases [17].
  • Other PTP inhibitors--orthovanadate and phenylarsine oxide (PAO)-inhibited PTPepsilon with IC50 values of 0.3 microM and 18 microM, respectively [3].
  • Complex formation was disrupted by vanadate, highlighting the importance of the PTP active site in the interaction and supporting the characterization of these proteins as substrates [18].
  • We have recently isolated a cDNA encoding a novel human receptor-type tyrosine phosphatase, termed PTP-RO (for a protein tyrosine phosphatase receptor omicron), from 5-fluorouracil-treated murine bone marrow cells [19].
  • Here we report that modulation of phosphotyrosine-dependent events with a protein tyrosine phosphatases (PTP) inhibitor, the peroxovanadium (pV) compound bpV(phen) (potassium bisperoxo(1,10-phenanthroline)oxovanadate(Vi)), can control host-pathogen interactions by different mechanisms [20].
 

Regulatory relationships of Reg1

 

Other interactions of Reg1

  • The cellular extracts from neoislets were immunoreactive to anti-insulin antibody and expressed insulin, glucagon, GLUT-2, PDX-1 and Reg-1 genes [21].
 

Analytical, diagnostic and therapeutic context of Reg1

  • Using immunoprecipitation and gel filtration, we show that cyt-PTP epsilon forms dimers and higher-order associations in vivo, the first such demonstration among nonreceptor phosphatases [14].
  • Reciprocal immunoprecipitations and assays detected p59(fyn) and an appropriate kinase activity in PTPalpha immunoprecipitates and PTPalpha and PTP activity in p59(fyn) immunoprecipitates [22].
  • While parent M1 cells inoculated by intravenous injection formed metastatic tumors in the spleen, expression of PTP epsilon C suppressed tumor development in the spleen [23].
  • Lama is a PSP minigene and allows analysis of the PSP gene 5' regulatory region by transgenesis [24].
  • We have mapped the mouse protein tyrosine phosphatase epsilon (PTP epsilon, gene symbol Ptpre) gene to the distal region of chromosome 7 by linkage analysis using two sets of multilocus genetic crosses [25].

References

  1. Reg (regenerating) gene overexpression in islets from non-obese diabetic mice with accelerated diabetes: role of IFNbeta. Planas, R., Alba, A., Carrillo, J., Puertas, M.C., Ampudia, R., Pastor, X., Okamoto, H., Takasawa, S., Gurr, W., Pujol-Borrell, R., Verdaguer, J., Vives-Pi, M. Diabetologia (2006) [Pubmed]
  2. Host cell responses to Listeria monocytogenes infection include differential transcription of host stress genes involved in signal transduction. Schwan, W.R., Goebel, W. Proc. Natl. Acad. Sci. U.S.A. (1994) [Pubmed]
  3. Protein-tyrosine phosphatase activity regulates osteoclast formation and function: inhibition by alendronate. Schmidt, A., Rutledge, S.J., Endo, N., Opas, E.E., Tanaka, H., Wesolowski, G., Leu, C.T., Huang, Z., Ramachandaran, C., Rodan, S.B., Rodan, G.A. Proc. Natl. Acad. Sci. U.S.A. (1996) [Pubmed]
  4. Induction of the proliferative phenotype in differentiated myogenic cells by hypoxia. Butler, A.J., Eagleton, M.J., Wang, D., Howell, R.L., Strauch, A.R., Khasgiwala, V., Smith, H.C. J. Biol. Chem. (1991) [Pubmed]
  5. The Yersinia tyrosine phosphatase YopH targets a novel adhesion-regulated signalling complex in macrophages. Black, D.S., Marie-Cardine, A., Schraven, B., Bliska, J.B. Cell. Microbiol. (2000) [Pubmed]
  6. Hypomyelination and increased activity of voltage-gated K(+) channels in mice lacking protein tyrosine phosphatase epsilon. Peretz, A., Gil-Henn, H., Sobko, A., Shinder, V., Attali, B., Elson, A. EMBO J. (2000) [Pubmed]
  7. CD45 opposes beta-amyloid peptide-induced microglial activation via inhibition of p44/42 mitogen-activated protein kinase. Tan, J., Town, T., Mori, T., Wu, Y., Saxe, M., Crawford, F., Mullan, M. J. Neurosci. (2000) [Pubmed]
  8. Involvement of a mitochondrial phosphatase in the regulation of ATP production and insulin secretion in pancreatic beta cells. Pagliarini, D.J., Wiley, S.E., Kimple, M.E., Dixon, J.R., Kelly, P., Worby, C.A., Casey, P.J., Dixon, J.E. Mol. Cell (2005) [Pubmed]
  9. Cooperative inhibition of T-cell antigen receptor signaling by a complex between a kinase and a phosphatase. Cloutier, J.F., Veillette, A. J. Exp. Med. (1999) [Pubmed]
  10. The motheaten mutation rescues B cell signaling and development in CD45-deficient mice. Pani, G., Siminovitch, K.A., Paige, C.J. J. Exp. Med. (1997) [Pubmed]
  11. PTP alpha regulates integrin-stimulated FAK autophosphorylation and cytoskeletal rearrangement in cell spreading and migration. Zeng, L., Si, X., Yu, W.P., Le, H.T., Ng, K.P., Teng, R.M., Ryan, K., Wang, D.Z., Ponniah, S., Pallen, C.J. J. Cell Biol. (2003) [Pubmed]
  12. Differences in phosphatase modulation of alpha4beta1 and alpha5beta1 integrin-mediated adhesion and migration of B16F1 cells. Hangan-Steinman, D., Ho, W.C., Shenoy, P., Chan, B.M., Morris, V.L. Biochem. Cell Biol. (1999) [Pubmed]
  13. Identification of a cytoplasmic, phorbol ester-inducible isoform of protein tyrosine phosphatase epsilon. Elson, A., Leder, P. Proc. Natl. Acad. Sci. U.S.A. (1995) [Pubmed]
  14. Dimerization in vivo and inhibition of the nonreceptor form of protein tyrosine phosphatase epsilon. Toledano-Katchalski, H., Tiran, Z., Sines, T., Shani, G., Granot-Attas, S., den Hertog, J., Elson, A. Mol. Cell. Biol. (2003) [Pubmed]
  15. Activation of the Reg family genes by pancreatic-specific IGF-I gene deficiency and after streptozotocin-induced diabetes in mouse pancreas. Lu, Y., Ponton, A., Okamoto, H., Takasawa, S., Herrera, P.L., Liu, J.L. Am. J. Physiol. Endocrinol. Metab. (2006) [Pubmed]
  16. Differentially expressed proteins in the pancreas of diet-induced diabetic mice. Qiu, L., List, E.O., Kopchick, J.J. Mol. Cell Proteomics (2005) [Pubmed]
  17. The role of protein tyrosine phosphatase 1B in Ras signaling. Dubé, N., Cheng, A., Tremblay, M.L. Proc. Natl. Acad. Sci. U.S.A. (2004) [Pubmed]
  18. Epidermal growth factor receptor and the adaptor protein p52Shc are specific substrates of T-cell protein tyrosine phosphatase. Tiganis, T., Bennett, A.M., Ravichandran, K.S., Tonks, N.K. Mol. Cell. Biol. (1998) [Pubmed]
  19. The receptor protein tyrosine phosphatase, PTP-RO, is upregulated during megakaryocyte differentiation and Is associated with the c-Kit receptor. Taniguchi, Y., London, R., Schinkmann, K., Jiang, S., Avraham, H. Blood (1999) [Pubmed]
  20. Modulation of interferon-gamma-induced macrophage activation by phosphotyrosine phosphatases inhibition. Effect on murine Leishmaniasis progression. Olivier, M., Romero-Gallo, B.J., Matte, C., Blanchette, J., Posner, B.I., Tremblay, M.J., Faure, R. J. Biol. Chem. (1998) [Pubmed]
  21. Analysis of morphological and functional maturation of neoislets generated in vitro from pancreatic ductal cells and their suitability for islet banking and transplantation. Katdare, M.R., Bhonde, R.R., Parab, P.B. J. Endocrinol. (2004) [Pubmed]
  22. Physical and functional interactions between receptor-like protein-tyrosine phosphatase alpha and p59fyn. Bhandari, V., Lim, K.L., Pallen, C.J. J. Biol. Chem. (1998) [Pubmed]
  23. Reduced tumorigenicity of murine leukemia cells expressing protein-tyrosine phosphatase, PTPepsilon C. Tanuma, N., Shima, H., Shimada, S., Kikuchi, K. Oncogene (2003) [Pubmed]
  24. Tissue-specific expression in the salivary glands of transgenic mice. Mikkelsen, T.R., Brandt, J., Larsen, H.J., Larsen, B.B., Poulsen, K., Ingerslev, J., Din, N., Hjorth, J.P. Nucleic Acids Res. (1992) [Pubmed]
  25. The protein tyrosine phosphatase epsilon gene maps to mouse chromosome 7 and human chromosome 10q26. Elson, A., Kozak, C.A., Morton, C.C., Weremowicz, S., Leder, P. Genomics (1996) [Pubmed]
 
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