Serine/threonine-protein kinase PAK 6 is an enzyme that in humans is encoded by the PAK6 gene. [5] [6]
PAK6 belongs to the Group II PAK family members. [7] Like other family members, PAK6 is also evolutionary conserved across species. [8]
Serine/threonine-protein kinase PAK 6 is an enzyme that in humans is encoded by the PAK6 gene. [5] [6]
PAK6 belongs to the Group II PAK family members. [7] Like other family members, PAK6 is also evolutionary conserved across species. [8]
The PAK6 was originally cloned as an androgen receptor interacting kinase which can be stimulated by androgen receptor but not Rac or Cdc42, like other family members. [7]
The human PAK6 gene consists of 16 exons of which 8 exons are used for 5’-UTR splicing to generating 17 transcripts by alternative splicing, and the gene is about 38-kb long. Among PAK6 transcripts, 14 are protein coding RNAs to code four proteins of 681 and 636 amino acids while remaining PAK6 transcripts are non-coding RNAs. There are five transcripts in murine PAK6 gene, of which two transcripts are protein coding and other two non-coding RNAs(Gene from review).
Following the general structural organization of the group II PAKs, PAK6 also contains a kinase, and a GTPase interacting domain. [9] [10]
This gene encodes a protein that shares a high degree of sequence similarity with p21-activated kinase (PAK) family members. The proteins of this family are Rac/Cdc42-associated Ste20-like Ser/Thr protein kinases, characterized by a highly conserved amino-terminal Cdc42/Rac interactive binding (CRIB) domain and a carboxyl-terminal kinase domain. PAK kinases are implicated in the regulation of a number of cellular processes, including cytoskeleton rearrangement, apoptosis and the MAP kinase signaling pathway. The protein encoded by this gene was found to interact with androgen receptor (AR), which is a steroid hormone-dependent transcription factor that is important for male sexual differentiation and development. The p21-activated protein kinase 6 gene was found to be highly expressed in testis and prostate tissues and the encoded protein was shown to cotranslocate into the nucleus with AR in response to androgen. [6]
Genetic deletion of PAK6 alone in mice leads to increased body mass. [11] However, PAK6 deletion along with PAK5 impairs the ability of animals to learn and move. [11] [12] PAK6 expression is increased in a rat model of spinal cord injury. [13] PAK6 is also considered a candidate gene for epileptic encephalopathy, [14] and interacts with Parkinson associated gene product leucine-rich repeat kinase 2. [15] PAK6 expression has been found to be overexpressed in prostate cancer, [16] [17] hepatocellular carcinoma, [18] and colon cancer. [19] PAK6 levels have been correlated well with therapeutic resistance to 5-flurouracil, [19] docetaxel, [17] and radiation. [20]
PAK6 kinase activity is positively regulated by androgen receptor, [7] [21] p38MAPK, [22] 5-fluorouracil [19] and atypical Rho family GTPase Chp/RhoV. [23] PAK6 expression is negatively regulated by miR-328, miR-429 and miR-23a. [24] [25] [26] PAK6 interacts with junctional protein IQGAP1, [27] [28] E3 ligase Mdm2, [29] and leucine-rich repeat kinase 2 (LRRK2). [15]
PAK6 has been shown to interact with Androgen receptor. [5] [7]
 | The 2016 version of this article was updated by an external expert under a dual publication model. The corresponding academic peer reviewed article was published in Gene and can be cited as: Rakesh Kumar; Rahul Sanawar; Xiaodong Li; Feng Li (19 December 2016). "Structure, biochemistry, and biology of PAK kinases". Gene . Gene Wiki Review Series. 605: 20–31. doi:10.1016/J.GENE.2016.12.014. ISSN 0378-1119. PMC 5250584 . PMID 28007610. Wikidata Q38779105. |
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