Disease relevance of Ptpns1

• A CD47-Fc fusion protein or antibodies to SHPS-1 inhibited migration of human melanoma cells or of CHO cells overexpressing SHPS-1 [1].
• LAP-induced tyrosine phosphorylation of SHPS-1 was inhibited by Clostridium botulinum C3 exoenzyme (which inactivates RHO) but not by pertussis toxin [2].

High impact information on Ptpns1

• Overexpression of wild-type SHPS-1 promoted CHO cell migration, whereas expression of the SHPS-1-4F mutant, which lacks the phosphorylation sites required for SHP-2 binding, had no effect [1].
• Role of the CD47-SHPS-1 system in regulation of cell migration [1].
• Signal regulatory protein alpha ligation induces macrophage nitric oxide production through JAK/STAT- and phosphatidylinositol 3-kinase/Rac1/NAPDH oxidase/H2O2-dependent pathways [3].
• Signal regulatory protein alpha (SIRPalpha) is a glycoprotein receptor that recruits and signals via the tyrosine phosphatases SHP-1 and SHP-2 [3].
• SIRPalpha-induced NO production was prevented by inhibition of the tyrosine kinase JAK2 [3].

Biological context of Ptpns1

• Various mitogens, including serum, insulin, and lysophosphatidic acid, or cell adhesion induced tyrosine phosphorylation of SHPS-1 and its subsequent association with SHP-2 in cultured cells [4].
• In macrophages SIRPalpha can negatively regulate the phagocytosis of host cells and the production of tumor necrosis factor alpha [3].
• A novel membrane glycoprotein, SHPS-1, that binds the SH2-domain-containing protein tyrosine phosphatase SHP-2 in response to mitogens and cell adhesion [4].
• Furthermore, we observed that co-expression of CD47/IAP with BIT/SHPS-1 enhanced neuronal cell death, and that BDNF prevented it [5].
• Previously, we demonstrated that the neuronal adhesion molecule brain immunoglobulin-like molecule with tyrosine-based activation motifs/SHP substrate 1 (BIT/SHPS-1) is involved in brain-derived neurotrophic factor (BDNF)-promoted neuronal cell survival [5].

Anatomical context of Ptpns1

• The exposure of monocytes to elastic laminae induced activation of SIRP alpha, which in turn activated SHP-1 [6].
• SHPS-1 is highly expressed in brain, but at much lower levels in skeletal muscle [7].
• Immunohistochemistry revealed SHPS-1 immunoreactivity at neuromuscular junctions (NMJs) under innervation, whereas immunoreactivity was observed extrasynaptically in muscle fibers after denervation [7].
• Antibodies to SHPS-1 failed to inhibit migration of CHO cells expressing SHPS-1-4F [1].
• However, unlike Src, focal adhesion kinase did not catalyze phosphorylation of the cytoplasmic domain of SHPS-1 in vitro [8].

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

• BIT/SHPS-1 enhances brain-derived neurotrophic factor-promoted neuronal survival in cultured cerebral cortical neurons [10].

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

• Ligation of SIRPalpha by antibodies or soluble CD47 triggers inducible nitric oxide synthase expression and production of NO [3].
• Denervation enhances the expression of SHPS-1 in rat skeletal muscle [7].
• Western blot analysis also confirmed the increase of SHPS-1 in denervated muscle [7].
• Crystallization and preliminary X-ray analysis of rat SHPS-1 [14].

References