Focal adhesion kinase and Proline-rich tyrosine kinase 2 (FAK/PYK2)

Focal adhesion kinase (FAK, encoded by the PTK2 gene) and proline-rich tyrosine kinase 2 (PYK2, encoded by the PTK2B gene) are closely related, non-receptor tyrosine kinases involved in regulating cell adhesion, migration, proliferation, and survival[1][2][5][6]. Both molecules share a similar domain architecture—N-terminal FERM domain, central kinase domain, and C-terminal focal adhesion targeting domain—and act as scaffolds at focal adhesion sites, transducing signals from integrins and growth factor receptors to intracellular pathways[2][4]. FAK is ubiquitously expressed in most cells, whereas PYK2 has more restricted, tissue-specific expression and calcium-responsive signaling[5]. Both are strongly implicated in human disease, especially cancer, where their overactivation drives tumor growth, survival, metastasis, and drug resistance, making them attractive therapeutic targets[1][5]. Multiple small-molecule inhibitors targeting FAK are in clinical development for oncology indications, with emerging interest in selective PYK2 targeting for distinct disease contexts[5][6][7].

Other names

PTK2Protein tyrosine kinase 2FAK1PTK2BProtein tyrosine kinase 2-betaCADTKRAFTKFAK2fakB

Inhibition of kinase activity (e.g., blocking ATP binding site), Disruption of protein-protein interactions/scaffolding function, Blocking autophosphorylation and downstream signal transduction.