SFK activity is reciprocally regulated by Csk and CD45

Phosphorylation of a c-terminal tail negative regulatory tyrosine of SFKs by Csk facilitates its interaction with its SH2 domain, resulting in a closed, catalytically inactive conformation. Dephosphorylation of this site by CD45 favors an open conformation. Phosphorylation of the catalytic site tyrosine is required for full kinase activity. CD45 and PEP can negatively regulate SFK activity by dephosphorylating the catalytic site tyrosine.