PAK3

PAK proteins are critical effectors that link Rho GTPases to cytoskeleton reorganization and nuclear signaling. PAK proteins, a family of serine/threonine p21-activating kinases, serve as targets for the small GTP binding proteins Cdc42 and RAC and have been implicated in a wide range of biological activities. The protein encoded by this gene forms an activated complex with GTP-bound RAS-like (P21), CDC2 and RAC1 proteins which then catalyzes a variety of targets. This protein may be necessary for dendritic development and for the rapid cytoskeletal reorganization in dendritic spines associated with synaptic plasticity. Defects in this gene are the cause of non-syndromic mental retardation X-linked type 30 (MRX30), also called X-linked mental retardation type 47 (MRX47). Alternatively spliced transcript variants encoding different isoforms have been identified. [provided by RefSeq]

Full Name

p21 protein (Cdc42/Rac)-activated kinase 3

Function

Serine/threonine protein kinase that plays a role in a variety of different signaling pathways including cytoskeleton regulation, cell migration, or cell cycle regulation. Plays a role in dendrite spine morphogenesis as well as synapse formation and plasticity. Acts as downstream effector of the small GTPases CDC42 and RAC1. Activation by the binding of active CDC42 and RAC1 results in a conformational change and a subsequent autophosphorylation on several serine and/or threonine residues. Phosphorylates MAPK4 and MAPK6 and activates the downstream target MAPKAPK5, a regulator of F-actin polymerization and cell migration. Additionally, phosphorylates TNNI3/troponin I to modulate calcium sensitivity and relaxation kinetics of thin myofilaments. May also be involved in early neuronal development. 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).

Biological Process

AxonogenesisISS:UniProtKB
Cellular response to organic cyclic compoundIEA:Ensembl
Dendrite developmentISS:UniProtKB
Dendritic spine morphogenesisISS:UniProtKB
Ephrin receptor signaling pathwayTAS:Reactome
Intracellular signal transductionManual Assertion Based On ExperimentIBA:GO_Central
Positive regulation of dendritic spine morphogenesisIEA:Ensembl
Positive regulation of DNA biosynthetic processIEA:Ensembl
Positive regulation of fibroblast migrationIEA:Ensembl
Positive regulation of neuron apoptotic processIEA:Ensembl
Protein phosphorylationManual Assertion Based On ExperimentIBA:GO_Central
Regulation of actin cytoskeleton organizationManual Assertion Based On ExperimentIBA:GO_Central
Regulation of actin filament polymerizationManual Assertion Based On ExperimentIDA:UniProtKB
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
Synapse organizationManual Assertion Based On ExperimentTAS:UniProtKB

Cellular Location

Cytoplasm

Involvement in disease

Intellectual developmental disorder, X-linked 30 (XLID30):
A disorder characterized by significantly below average general intellectual functioning associated with impairments in adaptive behavior and manifested during the developmental period. Intellectual deficiency is the only primary symptom of non-syndromic X-linked mental retardation, while syndromic mental retardation presents with associated physical, neurological and/or psychiatric manifestations.

PTM

Autophosphorylated when activated by CDC42/p21.
Neddylated.