PAK3
Description
The PAK3 (p21 (RAC1) activated kinase 3) is a protein-coding gene located on chromosome X.
PAK3 (p21-activated kinase 2, beta-PAK) is one of three members of Group I PAK family of evolutionary conserved serine/threonine kinases. PAK3 is preferentially expressed in neuronal cells and involved in synapse formation and plasticity and mental retardation. PAK3 was initially cloned from a murine fibroblast cDNA library and from a murine embryo cDNA library. Like other group I PAKs, PAK3 is stimulated by activated Cdc42 and Rac1. The human PAK3 gene, the longest group I family member, is 283-kb long. The PAK3 gene is composed of 22 exons of which 6 exons are for 5’-UTR and generates 13 alternative spliced transcripts. Among PAK3 transcripts, 11 transcripts are for coding proteins ranging from 181- to 580-amino acids long, while remaining two transcripts are non-coding RNAs. The murine PAK3 gene contains 10 transcripts, coding six proteins from 544 amino acids and 559 amino acids long, and four smaller polypeptides from 23 to 366 amino acids. Similar to PAK1, PAK2 contains a p21-binding domain (PBD) and an auto-inhibitory domain (AID) and exists in an inactive conformation. PAK3 activity is stimulated by Dbl, Cdc42 and Cool-2, and by AP1 transcription factor.
PAK3 is a serine/threonine protein kinase that plays a role in various signaling pathways, including cytoskeleton regulation, cell migration, and cell cycle regulation. It is involved in dendrite spine morphogenesis, synapse formation, and plasticity, acting as a downstream effector of the small GTPases CDC42 and RAC1. Activation by active CDC42 and RAC1 triggers a conformational change and autophosphorylation on serine/threonine residues. PAK3 phosphorylates MAPK4 and MAPK6, activating MAPKAPK5, a regulator of F-actin polymerization and cell migration. It also phosphorylates TNNI3/troponin I to modulate calcium sensitivity and relaxation kinetics of thin myofilaments. PAK3 might be involved in early neuronal development, as it is necessary for the formation of dendritic spines and excitatory synapses in hippocampal neurons. This function depends on its kinase activity and may involve the regulation of actomyosin contractility through phosphorylation of myosin II regulatory light chain (MLC).
PAK3 is also known as ARA, MRX30, MRX47, OPHN3, PAK-3, PAK3beta, XLID30, bPAK, beta-PAK.
