| First Author | Ohnishi H | Year | 2010 |
| Journal | J Neurosci | Volume | 30 |
| Issue | 31 | Pages | 10472-83 |
| PubMed ID | 20685990 | Mgi Jnum | J:162849 |
| Mgi Id | MGI:4820440 | Doi | 10.1523/JNEUROSCI.0257-10.2010 |
| Citation | Ohnishi H, et al. (2010) Stress-evoked tyrosine phosphorylation of signal regulatory protein alpha regulates behavioral immobility in the forced swim test. J Neurosci 30(31):10472-83 |
| abstractText | Severe stress induces changes in neuronal function that are implicated in stress-related disorders such as depression. The molecular mechanisms underlying the response of the brain to stress remain primarily unknown, however. Signal regulatory protein alpha (SIRPalpha) is an Ig-superfamily protein that undergoes tyrosine phosphorylation and binds the protein tyrosine phosphatase Shp2. Here we show that mice expressing a form of SIRPalpha that lacks most of the cytoplasmic region manifest prolonged immobility (depression-like behavior) in the forced swim (FS) test. FS stress induced marked tyrosine phosphorylation of SIRPalpha in the brain of wild-type mice through activation of Src family kinases. The SIRPalpha ligand CD47 was important for such SIRPalpha phosphorylation, and CD47-deficient mice also manifested prolonged immobility in the FS test. Moreover, FS stress-induced tyrosine phosphorylation of both the NR2B subunit of the NMDA subtype of glutamate receptor and the K+-channel subunit Kvbeta2 was regulated by SIRPalpha. Thus, tyrosine phosphorylation of SIRPalpha is important for regulation of depression-like behavior in the response of the brain to stress. |
