Fig. 2. The two-step activation model for Tec kinases. (1) In the first step, the PH domain interacts with the products of PI3K or, alternatively, with other binding partners (such as the FERM domain of FAK, heterotrimeric G-protein subunits, PKCs or F-actin) to translocate to the plasma membrane or specific intracellular microenvironments required for activation. (2) Once at the membrane, Tec kinases are phosphorylated on a tyrosine residue in their catalytic domain by SFKs.

Subsequently, a tyrosine residue in the SH3 domain is autophosphorylated, preventing further inhibitory intramolecular interactions. Phosphorylated tyrosine residues are illustrated as red stars.