Function
Protein kinase PAK1 is involved in intracellular signaling pathways downstream of integrins and receptor-type kinases. It plays a critical role in cytoskeleton dynamics, cell adhesion, migration, proliferation, apoptosis, mitosis, and vesicle-mediated transport processes. PAK1 directly phosphorylates BAD, protecting cells against apoptosis. It is activated upon interaction with CDC42 and RAC1, functioning as a GTPase effector that links the Rho-related GTPases CDC42 and RAC1 to the JNK MAP kinase pathway. PAK1 phosphorylates and activates MAP2K1, mediating downstream MAP kinase activation. It participates in the reorganization of the actin cytoskeleton, actin stress fibers, and focal adhesion complexes. PAK1 phosphorylates the tubulin chaperone TBCB, playing a role in the regulation of microtubule biogenesis and organization of the tubulin cytoskeleton. PAK1 also regulates insulin secretion in response to elevated glucose levels. It forms part of a ternary complex with PAK1, DVL1, and MUSK, essential for MUSK-dependent regulation of AChR clustering during neuromuscular junction (NMJ) formation. PAK1 activity is inhibited in apoptotic cells, potentially due to binding of CDC2L1 and CDC2L2. It phosphorylates MYL9/MLC2, RAF1 at 'Ser-338' and 'Ser-339', SNAI1 at 'Ser-246', and NR3C2 in podocytes. PAK1 is required for ACKR2-induced phosphorylation of LIMK1 and cofilin (CFL1), upregulating ACKR2 from endosomal compartment to cell membrane, enhancing its efficiency in chemokine uptake and degradation. In synapses, PAK1 seems to regulate F-actin cluster formation by SHANK3, possibly through CFL1 phosphorylation and inactivation. It contributes to RUFY3-mediated facilitation of gastric cancer cell migration and invasion. In response to DNA damage, PAK1 phosphorylates MORC2, activating its ATPase activity and promoting chromatin remodeling. In neurons, PAK1 plays a crucial role in regulating GABA(A) receptor synaptic stability and GABAergic inhibitory synaptic transmission through its role in F-actin stabilization. In hippocampal neurons, PAK1 is necessary for the formation of dendritic spines and excitatory synapses, a function dependent on kinase activity and potentially exerted by regulating actomyosin contractility through phosphorylation of myosin II regulatory light chain (MLC). Together with GIT1, PAK1 positively regulates microtubule nucleation during interphase.