Src
kinases are themselves regulated by alternative phosphorylation/dephosphorylation and ubiquitin-mediated degradation
•The ezymatic activity of the Src kinases themselves is regulated by phosphorylation of two different domains.
•Csk, a tyrosine kinase, regulates Src kinase activity by phosphorylating the inhibitory (carboxy) tyrosine residue.
•Conformational change blocks activating tyrosine
• To be effective,
Csk must be recruited to the inner surface
of the membrane by Cbp (Csk binding protein),
a transmembrane protein that must be phosphorylated
to be active. Src kinases phosphorylate
Cbp, and this pathway defines a negative
feedback loop following antigen stimulation.