Intramolecular interaction between phosphorylated tyrosine-783 and the C-terminal Src homology 2 domain activates phospholipase C-gamma1.

ABSTRACT: Phospholipase C-gamma1 (PLC-gamma1) contains two tandem Src homology 2 (SH2) domains. The NH(2)-terminal SH2 domain has been known to mediate the binding of PLC-gamma1 to receptor protein tyrosine kinases, which then activate PLC-gamma1 via phosphorylation at Y783. We now show that the phosphorylated Y783 residue (pY783) associates with the COOH-terminal SH2 domain [SH2(C)] within the same molecule of PLC-gamma1. The specificity of this intramolecular interaction is demonstrated in several ways. The mutation of SH2(C), but not of the NH(2)-terminal SH2 domain, exposes pY783 and makes it available for binding by anti-pY783 antibodies, for intermolecular association with a GST fusion protein containing the tandem SH2 domains of PLC-gamma1 and for dephosphorylation by phosphatases. The intram

SUBMITTER: Poulin B 

PROVIDER: S-EPMC555506 | biostudies-literature | 2005 Mar

REPOSITORIES: biostudies-literature