PAK3 (p21-activated kinase 2, beta-PAK) is one of three members of Group I PAK family of evolutionary conserved

serine/threonine kinases A serine/threonine protein kinase () is a kinase enzyme, in particular a protein kinase, that phosphorylates the OH group of the amino-acid residues serine or threonine, which have similar side chains. At least 350 of the 500+ human pr ...

. PAK3 is preferentially expressed in neuronal cells and involved in

synapse In the nervous system, a synapse is a structure that permits a neuron (or nerve cell) to pass an electrical or chemical signal to another neuron or to the target effector cell. Synapses are essential to the transmission of nervous impulses from ...

formation and plasticity and

mental retardation Intellectual disability (ID), also known as general learning disability in the United Kingdom and formerly mental retardation,Rosa's Law, Pub. L. 111-256124 Stat. 2643(2010). is a generalized neurodevelopmental disorder characterized by signific ...

Discovery

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.

Gene and spliced variants

The human PAK3 gene, the longest group I family member, is 283-kb long. The PAK3 gene is composed of 22

exons An exon is any part of a gene that will form a part of the final mature RNA produced by that gene after introns have been removed by RNA splicing. The term ''exon'' refers to both the DNA sequence within a gene and to the corresponding sequence ...

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 A non-coding RNA (ncRNA) is a functional RNA molecule that is not translated into a protein. The DNA sequence from which a functional non-coding RNA is transcribed is often called an RNA gene. Abundant and functionally important types of non- ...

. 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.

Protein domains

Similar to

PAK1 Serine/threonine-protein kinase PAK 1 is an enzyme that in humans is encoded by the ''PAK1'' gene. PAK1 is one of six members of the PAK family of serine/threonine kinases which are broadly divided into group I (PAK1, PAK2 and PAK3) and group II ...

, PAK2 contains a p21-binding domain (PBD) and an auto-inhibitory domain (AID) and exists in an inactive conformation.

Activators and inhibitors

PAK3 activity is stimulated by Dbl, Cdc42 and Cool-2, and by AP1 transcription factor. Stimulation of PAK3 activity by upstream stimulators such as Dbl or Cdc42 is inhibited by p50 (Cool-1) PAK3 activity is inhibited by FRAX597, a PAN inhibitor of PAKs.

Functions

PAK3 is overexpressed in neuroendocrine/carcinoids

tumors A neoplasm () is a type of abnormal and excessive growth of tissue. The process that occurs to form or produce a neoplasm is called neoplasia. The growth of a neoplasm is uncoordinated with that of the normal surrounding tissue, and persists ...

. PAK3 has been shown to be important for synapse formation and plasticity, and contribute to mental retardation. Further, every mutations in the PAK3 gene have been associated with nonsyndromic X-linked mental retardation.

Notes

References

External links

* * {{PDBe-KB2, Q61036, Mouse Serine/threonine-protein kinase PAK 3