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Gene Review

Sirpa  -  signal-regulatory protein alpha

Rattus norvegicus

Synonyms: Bit, Brain Ig-like molecule with tyrosine-based activation motifs, CD172 antigen-like family member A, Inhibitory receptor SHPS-1, Macrophage fusion receptor, ...
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Disease relevance of Ptpns1


High impact information on Ptpns1


Biological context of Ptpns1


Anatomical context of Ptpns1


Associations of Ptpns1 with chemical compounds

  • SHPS-1 expression in SR3Y1 was restored by treatment with herbimycin A, a potent inhibitor of tyrosine kinase, or by the expression of dominant negative form of Ras [9].
  • In addition, LY294002, a specific inhibitor of phosphatidylinositol 3-kinase, blocked the enhancement of BDNF-promoted neuronal survival in both neurons expressing wild-type and 4F mutant BIT/SHPS-1 [10].
  • Together, these results suggest that insulin may induce phosphorylation of SHPS-1 at Tyr449 and Tyr473, to which SHP-2 then binds through its NH2-terminal and COOH-terminal SH2 domains, respectively [11].
  • The overexpression of wild-type SHPS-1, but not of a mutant SHPS-1 in which all four tyrosine residues in its cytoplasmic region were mutated to phenylalanine, markedly enhanced insulin-induced activation of mitogen-activated protein kinase in Chinese hamster ovary cells that overexpress the human insulin receptor [11].
  • Determination of amino acid sequences of peptides produced by endoproteinase digestion demonstrated that this 85-kDa mannose-rich glycoprotein component contained the SHP substrate-1 for phosphotyrosine phosphatases and at least one other member of the signal-regulatory protein (SIRP) family [12].

Regulatory relationships of Ptpns1


Other interactions of Ptpns1

  • Negative regulation of monocyte adhesion to arterial elastic laminae by signal regulatory protein alpha and Src homology 2 domain-containing protein-tyrosine phosphatase-1 [6].
  • Our results well support the evidence that Ret complexes within and outside rafts mediate distinct biological functions, and indicate that the presence of either Shps participates to determine such functions [13].

Analytical, diagnostic and therapeutic context of Ptpns1


  1. Role of the CD47-SHPS-1 system in regulation of cell migration. Motegi, S., Okazawa, H., Ohnishi, H., Sato, R., Kaneko, Y., Kobayashi, H., Tomizawa, K., Ito, T., Honma, N., Bühring, H.J., Ishikawa, O., Matozaki, T. EMBO J. (2003) [Pubmed]
  2. Lysophosphatidic acid-induced association of SHP-2 with SHPS-1: roles of RHO, FAK, and a SRC family kinase. Takeda, H., Matozaki, T., Fujioka, Y., Takada, T., Noguchi, T., Yamao, T., Tsuda, M., Ochi, F., Fukunaga, K., Narumiya, S., Yamamoto, T., Kasuga, M. Oncogene (1998) [Pubmed]
  3. Signal regulatory protein alpha ligation induces macrophage nitric oxide production through JAK/STAT- and phosphatidylinositol 3-kinase/Rac1/NAPDH oxidase/H2O2-dependent pathways. Alblas, J., Honing, H., de Lavalette, C.R., Brown, M.H., Dijkstra, C.D., van den Berg, T.K. Mol. Cell. Biol. (2005) [Pubmed]
  4. A novel membrane glycoprotein, SHPS-1, that binds the SH2-domain-containing protein tyrosine phosphatase SHP-2 in response to mitogens and cell adhesion. Fujioka, Y., Matozaki, T., Noguchi, T., Iwamatsu, A., Yamao, T., Takahashi, N., Tsuda, M., Takada, T., Kasuga, M. Mol. Cell. Biol. (1996) [Pubmed]
  5. Expression of CD47/integrin-associated protein induces death of cultured cerebral cortical neurons. Koshimizu, H., Araki, T., Takai, S., Yokomaku, D., Ishikawa, Y., Kubota, M., Sano, S., Hatanaka, H., Yamada, M. J. Neurochem. (2002) [Pubmed]
  6. Negative regulation of monocyte adhesion to arterial elastic laminae by signal regulatory protein alpha and Src homology 2 domain-containing protein-tyrosine phosphatase-1. Liu, S.Q., Alkema, P.K., Tieché, C., Tefft, B.J., Liu, D.Z., Li, Y.C., Sumpio, B.E., Caprini, J.A., Paniagua, M. J. Biol. Chem. (2005) [Pubmed]
  7. Denervation enhances the expression of SHPS-1 in rat skeletal muscle. Mitsuhashi, H., Yoshikawa, A., Sasagawa, N., Hayashi, Y., Ishiura, S. J. Biochem. (2005) [Pubmed]
  8. Integrin-mediated tyrosine phosphorylation of SHPS-1 and its association with SHP-2. Roles of Fak and Src family kinases. Tsuda, M., Matozaki, T., Fukunaga, K., Fujioka, Y., Imamoto, A., Noguchi, T., Takada, T., Yamao, T., Takeda, H., Ochi, F., Yamamoto, T., Kasuga, M. J. Biol. Chem. (1998) [Pubmed]
  9. v-Src suppresses SHPS-1 expression via the Ras-MAP kinase pathway to promote the oncogenic growth of cells. Machida, K., Matsuda, S., Yamaki, K., Senga, T., Thant, A.A., Kurata, H., Miyazaki, K., Hayashi, K., Okuda, T., Kitamura, T., Hayakawa, T., Hamaguchi, M. Oncogene (2000) [Pubmed]
  10. BIT/SHPS-1 enhances brain-derived neurotrophic factor-promoted neuronal survival in cultured cerebral cortical neurons. Araki, T., Yamada, M., Ohnishi, H., Sano, S.I., Hatanaka, H. J. Neurochem. (2000) [Pubmed]
  11. Roles of the complex formation of SHPS-1 with SHP-2 in insulin-stimulated mitogen-activated protein kinase activation. Takada, T., Matozaki, T., Takeda, H., Fukunaga, K., Noguchi, T., Fujioka, Y., Okazaki, I., Tsuda, M., Yamao, T., Ochi, F., Kasuga, M. J. Biol. Chem. (1998) [Pubmed]
  12. Prominent 85-kDa oligomannosidic glycoproteins of rat brain are signal regulatory proteins and include the SHP substrate-1 for tyrosine phosphatases. Bartoszewicz, Z.P., Jaffe, H., Sasaki, M., Möller, J.R., Stebbins, J.W., Gebrekristos, H., Quarles, R.H. J. Neurochem. (1999) [Pubmed]
  13. The Shp-1 and Shp-2, tyrosine phosphatases, are recruited on cell membrane in two distinct molecular complexes including Ret oncogenes. Incoronato, M., D'Alessio, A., Paladino, S., Zurzolo, C., Carlomagno, M.S., Cerchia, L., de Franciscis, V. Cell. Signal. (2004) [Pubmed]
  14. Crystallization and preliminary X-ray analysis of rat SHPS-1. Nagata, A., Ohnishi, H., Yoshimura, M., Ogawa, A., Ujita, S., Adachi, H., Okada, M., Matozaki, T., Nakagawa, A. Acta Crystallograph. Sect. F Struct. Biol. Cryst. Commun. (2006) [Pubmed]
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