PAK1

PAK proteins are critical effectors that link RhoGTPases to cytoskeleton reorganization and nuclear signaling. PAK proteins, a family of serine/threonine p21-activating kinases, include PAK1, PAK2, PAK3 and PAK4. These proteins serve as targets for the small GTP binding proteins Cdc42 and Rac and have been implicated in a wide range of biological activities. PAK1 regulates cell motility and morphology. Alternativelt spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq]

p21 protein (Cdc42/Rac)-activated kinase 1

Protein kinase involved in intracellular signaling pathways downstream of integrins and receptor-type kinases that plays an important role in cytoskeleton dynamics, in cell adhesion, migration, proliferation, apoptosis, mitosis, and in vesicle-mediated transport processes (PubMed:11896197, PubMed:30290153).
Can directly phosphorylate BAD and protects cells against apoptosis. Activated by interaction with CDC42 and RAC1. Functions as GTPase effector that links the Rho-related GTPases CDC42 and RAC1 to the JNK MAP kinase pathway. Phosphorylates and activates MAP2K1, and thereby mediates activation of downstream MAP kinases. Involved in the reorganization of the actin cytoskeleton, actin stress fibers and of focal adhesion complexes. Phosphorylates the tubulin chaperone TBCB and thereby plays a role in the regulation of microtubule biogenesis and organization of the tubulin cytoskeleton. Plays a role in the regulation of insulin secretion in response to elevated glucose levels. Part of a ternary complex that contains PAK1, DVL1 and MUSK that is important for MUSK-dependent regulation of AChR clustering during the formation of the neuromuscular junction (NMJ). Activity is inhibited in cells undergoing apoptosis, potentially due to binding of CDC2L1 and CDC2L2. Phosphorylates MYL9/MLC2. Phosphorylates RAF1 at 'Ser-338' and 'Ser-339' resulting in: activation of RAF1, stimulation of RAF1 translocation to mitochondria, phosphorylation of BAD by RAF1, and RAF1 binding to BCL2. Phosphorylates SNAI1 at 'Ser-246' promoting its transcriptional repressor activity by increasing its accumulation in the nucleus. In podocytes, promotes NR3C2 nuclear localization. Required for atypical chemokine receptor ACKR2-induced phosphorylation of LIMK1 and cofilin (CFL1) and for the up-regulation of ACKR2 from endosomal compartment to cell membrane, increasing its efficiency in chemokine uptake and degradation. In synapses, seems to mediate the regulation of F-actin cluster formation performed by SHANK3, maybe through CFL1 phosphorylation and inactivation. Plays a role in RUFY3-mediated facilitating gastric cancer cells migration and invasion (PubMed:25766321).
In response to DNA damage, phosphorylates MORC2 which activates its ATPase activity and facilitates chromatin remodeling (PubMed:23260667).
In neurons, plays a crucial role in regulating GABA(A) receptor synaptic stability and hence GABAergic inhibitory synaptic transmission through its role in F-actin stabilization (By similarity).
In hippocampal neurons, necessary for the formation of dendritic spines and excitatory synapses; this function is dependent on kinase activity and may be exerted by the regulation of actomyosin contractility through the phosphorylation of myosin II regulatory light chain (MLC) (By similarity).
Along with GIT1, positively regulates microtubule nucleation during interphase (PubMed:27012601).

Actin cytoskeleton reorganizationManual Assertion Based On ExperimentIDA:UniProtKB
Apoptotic processIEA:UniProtKB-KW
Branching morphogenesis of an epithelial tubeManual Assertion Based On ExperimentIMP:UniProtKB
Cell migrationManual Assertion Based On ExperimentIMP:MGI
Cellular response to DNA damage stimulusManual Assertion Based On ExperimentIDA:UniProtKB
Chromatin remodelingManual Assertion Based On ExperimentIDA:UniProtKB
Ephrin receptor signaling pathwayTAS:Reactome
ExocytosisIEA:UniProtKB-KW
Fc-gamma receptor signaling pathway involved in phagocytosisTAS:Reactome
Hepatocyte growth factor receptor signaling pathwayManual Assertion Based On ExperimentIMP:CAFA
Intracellular signal transductionManual Assertion Based On ExperimentIBA:GO_Central
Negative regulation of cell proliferation involved in contact inhibitionManual Assertion Based On ExperimentIMP:UniProtKB
Neuron projection morphogenesisISS:UniProtKB
PhosphorylationManual Assertion Based On ExperimentIDA:UniProtKB
Positive regulation of cell migrationManual Assertion Based On ExperimentIDA:UniProtKB
Positive regulation of cell population proliferationManual Assertion Based On ExperimentIMP:BHF-UCL
Positive regulation of intracellular estrogen receptor signaling pathwayManual Assertion Based On ExperimentIDA:UniProtKB
Positive regulation of JUN kinase activityManual Assertion Based On ExperimentIMP:UniProtKB
Positive regulation of microtubule nucleationManual Assertion Based On ExperimentIMP:UniProtKB
Positive regulation of microtubule polymerizationManual Assertion Based On ExperimentIMP:CAFA
Positive regulation of peptidyl-serine phosphorylationManual Assertion Based On ExperimentIDA:UniProtKB
Positive regulation of protein phosphorylationManual Assertion Based On ExperimentIMP:UniProtKB
Positive regulation of stress fiber assemblyManual Assertion Based On ExperimentIMP:UniProtKB
Protein autophosphorylationManual Assertion Based On ExperimentIDA:UniProtKB
Protein phosphorylationManual Assertion Based On ExperimentIDA:UniProtKB
Regulation of actin cytoskeleton organizationManual Assertion Based On ExperimentIBA:GO_Central
Regulation of axonogenesisManual Assertion Based On ExperimentIBA:GO_Central
Regulation of MAPK cascadeManual Assertion Based On ExperimentIBA:GO_Central
Stimulatory C-type lectin receptor signaling pathwayTAS:Reactome
Wound healingManual Assertion Based On ExperimentIMP:UniProtKB

Cytoplasm
Cell junction, focal adhesion
Cell projection, lamellipodium
Cell membrane
Cell projection, ruffle membrane
Cell projection, invadopodium
Nucleus, nucleoplasm
Chromosome
Cytoplasm, cytoskeleton, microtubule organizing center, centrosome
Colocalizes with RUFY3, F-actin and other core migration components in invadopodia at the cell periphery (PubMed:25766321).
Recruited to the cell membrane by interaction with CDC42 and RAC1. Recruited to focal adhesions upon activation. Colocalized with CIB1 within membrane ruffles during cell spreading upon readhesion to fibronectin. Upon DNA damage, translocates to the nucleoplasm when phosphorylated at Thr-212 where is co-recruited with MORC2 on damaged chromatin (PubMed:23260667).
Localization to the centrosome does not depend upon the presence of gamma-tubulin (PubMed:27012601).
Localization of the active, but not inactive, protein to the adhesions and edge of lamellipodia is mediated by interaction with GIT1 (PubMed:11896197).

Intellectual developmental disorder with macrocephaly, seizures, and speech delay (IDDMSSD):
An autosomal dominant neurodevelopmental disorder characterized by impaired intellectual development, poor speech, postnatal macrocephaly, and seizures.

Autophosphorylated in trans, meaning that in a dimer, one kinase molecule phosphorylates the other one. Activated by autophosphorylation at Thr-423 in response to a conformation change, triggered by interaction with GTP-bound CDC42 or RAC1. Activated by phosphorylation at Thr-423 by BRSK2 and by PDPK1. Phosphorylated by JAK2 in response to PRL; this increases PAK1 kinase activity. Phosphorylated at Ser-21 by PKB/AKT; this reduces interaction with NCK1 and association with focal adhesion sites. Upon DNA damage, phosphorylated at Thr-212 and translocates to the nucleoplasm (PubMed:23260667).
Phosphorylated at tyrosine residues, which can be enhanced by NTN1 (By similarity).