PAK2 Gene - p21 Activated Kinase 2: Function, Mutations, and Disease

PAK2 (p21 activated kinase 2) encodes a member of the PAK family of serine/threonine kinases. This protein is activated by the binding of small GTPases (CDC42 and RAC1) and plays a critical role in regulating cell motility, morphology, survival, and apoptosis. PAK2 is ubiquitously expressed and is involved in both pro-survival signaling and caspase-mediated cleavage leading to cell death. Dysregulation of PAK2 is associated with various cancers and developmental disorders.

Tissue Expression

Cell Line Expression

Hotspot Mutations

Mutation functional classification

• RAC1/CDC42-PAK signaling

• MAPK/ERK pathway

• Apoptosis (caspase-mediated PAK2 cleavage)

• Regulation of actin cytoskeleton

PAK2 is a 524-amino acid serine/threonine kinase with an N-terminal regulatory domain containing a p21-binding domain (PBD) and an autoinhibitory domain, and a C-terminal kinase domain. It is activated by binding to active GTP-bound CDC42 or RAC1, leading to autophosphorylation and conformational change. PAK2 regulates cytoskeletal dynamics, cell motility, and survival. During apoptosis, PAK2 is cleaved by caspase-3, generating a constitutively active fragment that promotes cell death. The protein is ubiquitously expressed and localizes to the cytoplasm and membrane.