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Protein tyrosine phosphatase Shp2 positively regulates cold stress-induced tyrosine phosphorylation of SIRPα in neurons
- Source :
- Biochemical and Biophysical Research Communications. 569:72-78
- Publication Year :
- 2021
- Publisher :
- Elsevier BV, 2021.
-
Abstract
- The membrane protein SIRPα is a cold stress-responsive signaling molecule in neurons. Cold stress directly induces tyrosine phosphorylation of SIRPα in its cytoplasmic region, and phosphorylated SIRPα is involved in regulating experience-dependent behavioral changes in mice. Here, we examined the mechanism of cold stress-induced SIRPα phosphorylation in vitro and in vivo. The levels of activated Src family protein tyrosine kinases (SFKs), which phosphorylate SIRPα, were not increased by lowering the temperature in cultured neurons. Although the SFK inhibitor dasatinib markedly reduced SIRPα phosphorylation, low temperature induced an increase in SIRPα phosphorylation even in the presence of dasatinib, suggesting that SFK activation is not required for low temperature-induced SIRPα phosphorylation. However, in the presence of pervanadate, a potent inhibitor of protein tyrosine phosphatases (PTPases), SIRPα phosphorylation was significantly reduced by lowering the temperature, suggesting that either the inactivation of PTPase(s) that dephosphorylate SIRPα or increased protection of phosphorylated SIRPα from the PTPase activity is important for low temperature-induced SIRPα phosphorylation. Inactivation of PTPase Shp2 by the allosteric Shp2 inhibitor SHP099, but not by the competitive inhibitor NSC-87877, reduced SIRPα phosphorylation in cultured neurons. Shp2 knockout also reduced SIRPα phosphorylation in the mouse brain. Our data suggest that Shp2, but not SFKs, positively regulates cold stress-induced SIRPα phosphorylation in a PTPase activity-independent manner.
- Subjects :
- inorganic chemicals
Immunoblotting
Allosteric regulation
Dasatinib
Biophysics
Mice, Transgenic
Protein Tyrosine Phosphatase, Non-Receptor Type 11
macromolecular substances
Protein tyrosine phosphatase
environment and public health
Biochemistry
chemistry.chemical_compound
Piperidines
medicine
Animals
Phosphorylation
Receptors, Immunologic
Protein Kinase Inhibitors
Molecular Biology
Cells, Cultured
Cold stress
Mice, Knockout
Neurons
Chemistry
Cold-Shock Response
Tyrosine phosphorylation
Cell Biology
Cell biology
Cold Temperature
enzymes and coenzymes (carbohydrates)
Pyrimidines
medicine.anatomical_structure
Membrane protein
Tyrosine
bacteria
Neuron
medicine.drug
Subjects
Details
- ISSN :
- 0006291X
- Volume :
- 569
- Database :
- OpenAIRE
- Journal :
- Biochemical and Biophysical Research Communications
- Accession number :
- edsair.doi.dedup.....5fd1ed49114fc2a53388809a8b0a8249