Abstract 1565 Deciphering the reciprocal regulation of the Pyk2–Src activation complex

Pyk2 is a non-receptor tyrosine kinase that undergoes a multistep conformational rearrangement to achieve activation. The multi-domain protein is maintained in an autoinhibitory state by FERM interactions with the kinase. Clustering of Pyk2 and FERM disengagement allows for trans autophosphorylation of the FERM–kinase linker. Phosphorylated Pyk2 linker serves as a scaffold for Src recruitment. While it is well-established that the Pyk2–Src complex promotes Src-mediated phosphorylation of the Pyk2 activation loop, the downstream impacts on Src remain unclear.