PAK5

PAK5, or p21-activated kinase 5, is a serine/threonine kinase that belongs to the p21-activated kinase (PAK) family. It is categorized as a group II PAK, which includes PAK4 and PAK6, in contrast to the group I PAKs (PAK1–PAK3). The protein contains a regulatory region that binds Cdc42 or Rac1 through a CRIB motif and a catalytic kinase domain, with regulatory elements that modulate its activity.

Expression studies indicate that PAK5 is predominantly expressed in the brain, with detectable levels in other tissues as well. In neurons, the protein localizes to cytoplasmic compartments and can associate with synaptic structures, where it is thought to influence signaling related to neuronal morphology and connectivity.

Activation of PAK5 is driven by binding of active Rho family GTPases, particularly Cdc42 and Rac1. Binding relieves autoinhibitory constraints, enabling kinase activity. Once active, PAK5 participates in signaling networks that regulate cytoskeletal dynamics, vesicle transport, and cell morphology. Through phosphorylation of downstream effectors involved in actin regulation and microtubule stability, PAK5 contributes to processes such as neuronal development, synaptic plasticity, and, in certain contexts, cell migration and survival.

In cancer and other diseases, altered PAK5 expression or activity has been observed in some tumors, and the kinase is studied as a potential therapeutic target. Research has utilized inhibitors and gene-silencing approaches to probe its function and assess clinical relevance, though widely approved clinical applications remain limited. Overall, PAK5 is considered part of the broader PAK signaling network that coordinates cytoskeletal organization and cellular behavior.