First Author | Jingu D | Year | 2021 |
Journal | Biochem Biophys Res Commun | Volume | 569 |
Pages | 72-78 | PubMed ID | 34237430 |
Mgi Jnum | J:310462 | Mgi Id | MGI:6762341 |
Doi | 10.1016/j.bbrc.2021.06.084 | Citation | Jingu D, et al. (2021) Protein tyrosine phosphatase Shp2 positively regulates cold stress-induced tyrosine phosphorylation of SIRPalpha in neurons. Biochem Biophys Res Commun 569:72-78 |
abstractText | The membrane protein SIRPalpha is a cold stress-responsive signaling molecule in neurons. Cold stress directly induces tyrosine phosphorylation of SIRPalpha in its cytoplasmic region, and phosphorylated SIRPalpha is involved in regulating experience-dependent behavioral changes in mice. Here, we examined the mechanism of cold stress-induced SIRPalpha phosphorylation in vitro and in vivo. The levels of activated Src family protein tyrosine kinases (SFKs), which phosphorylate SIRPalpha, were not increased by lowering the temperature in cultured neurons. Although the SFK inhibitor dasatinib markedly reduced SIRPalpha phosphorylation, low temperature induced an increase in SIRPalpha phosphorylation even in the presence of dasatinib, suggesting that SFK activation is not required for low temperature-induced SIRPalpha phosphorylation. However, in the presence of pervanadate, a potent inhibitor of protein tyrosine phosphatases (PTPases), SIRPalpha phosphorylation was significantly reduced by lowering the temperature, suggesting that either the inactivation of PTPase(s) that dephosphorylate SIRPalpha or increased protection of phosphorylated SIRPalpha from the PTPase activity is important for low temperature-induced SIRPalpha phosphorylation. Inactivation of PTPase Shp2 by the allosteric Shp2 inhibitor SHP099, but not by the competitive inhibitor NSC-87877, reduced SIRPalpha phosphorylation in cultured neurons. Shp2 knockout also reduced SIRPalpha phosphorylation in the mouse brain. Our data suggest that Shp2, but not SFKs, positively regulates cold stress-induced SIRPalpha phosphorylation in a PTPase activity-independent manner. |