Phosphoprotein associated with glycosphingolipid-enriched microdomains differentially modulates SRC kinase activity in brain maturation.

摘要: Src family kinases (SFK) control multiple processes during brain development and function. We show here that the phosphoprotein associated with glycosphigolipid-enriched microdomains (PAG)/Csk binding protein (Cbp) modulates SFK activity in brain. The timing localization of PAG expression overlap Fyn Src, both which we find to PAG. demonstrate newborn (P1) mice negatively regulates (SFK). P1 Pag1(-/-) mouse brains decreased recruitment Csk into lipid rafts, reduced phosphorylation inhibitory tyrosines within SFKs, an increase >/ = 50%. While mice, are highly ubiquitously expressed, little is found adult suggesting altered modes regulation. In Pag1-deficiency has no effect upon Csk-distribution or tyrosine phosphorylation, but kinase now (-20-30%), pointing a compensatory mechanism may involve PSD93. distribution Csk-homologous CHK not altered. Importantly, since activities thus presenting reversed phenotype P1, this provides first vivo evidence for Csk-independent positive regulatory function