Figure 1.

Proto-oncogene tyrosine-protein kinase SRC (SRC) changes its conformation upon activation. (A) Closed inactive SRC under normal cellular conditions. Y530, located in the C-terminal tail of SRC, is phosphorylated and binds to the SH2 SRC domain, thereby blocking the catalytic site necessary for kinase activation. (B) Active SRC. When Y530 is dephosphorylated, displacement of the SH2/SH3 domains allows (auto)phosphorylation of Y419 and activation of SRC. Variants located near Y530, such as the germline E527K variant, disturb the SH2–Y530 interaction and also result in continuous SRC activation.