Focal adhesion kinase and Protein-tyrosine kinase 2-beta (FAK and Pyk2)

Focal adhesion kinase (FAK) and protein-tyrosine kinase 2-beta (Pyk2) are closely related, non-receptor tyrosine kinases that share similar domain architecture (N-terminal FERM domain, central kinase domain, C-terminal focal adhesion targeting domain), and act as key regulators of cellular adhesion, migration, proliferation, and survival. FAK is ubiquitously expressed and essential for embryonic development, while Pyk2 is highly expressed in brain and hematopoietic cells; both function as signaling hubs and scaffolds, integrating extracellular cues via phosphorylation and docking interactions. Dysregulation of FAK and/or Pyk2 is linked to cancer progression, metastasis, inflammatory responses, and neurodegeneration. Multiple small-molecule inhibitors targeting FAK (and, to a lesser extent, Pyk2) are in preclinical and clinical development for oncology and other indications.

Other names

Focal adhesion kinaseprotein-tyrosine kinase 2 (PTK2)FADKFAK1Protein-tyrosine kinase 2-betaPTK2BProline-rich tyrosine kinase 2RAFTKCADTKFAK2

Kinase inhibition: Most small molecules inhibit autophosphorylation of a pivotal tyrosine residue (Y397 in FAK, Y402 in Pyk2), disrupting downstream recruitment and activation of Src kinases and other adaptor proteins. Impairment of protein-protein interactions: Both proteins act as molecular scaffolds; some drugs aim to modulate these interactions.