Serine/threonine-protein kinase PAK 6 is an enzyme that in humans is encoded by the PAK6gene.[5][6]
PAK6 belongs to the Group II PAK family members.[7] Like other family members, PAK6 is also evolutionary conserved across species.[8]
Discovery
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]
Gene and spliced variants
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).
Protein domains
Following the general structural organization of the group II PAKs, PAK6 also contains a kinase, and a GTPase interacting domain.[9][10]
Function
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]
Regulators and interactors
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]
↑ Zhao W, Yang J, Shi W, Wu X, Shao B, Wu Q, Chen J, Ni L (June 2011). "Upregulation of p21-activated Kinase 6 in rat brain cortex after traumatic brain injury". Journal of Molecular Histology. 42 (3): 195–203. doi:10.1007/s10735-011-9324-8. PMID21541790. S2CID23042073.
↑ Kaur R, Yuan X, Lu ML, Balk SP (October 2008). "Increased PAK6 expression in prostate cancer and identification of PAK6 associated proteins". The Prostate. 68 (14): 1510–6. doi:10.1002/pros.20787. PMID18642328. S2CID12959176.
1 2 Wen X, Li X, Liao B, Liu Y, Wu J, Yuan X, Ouyang B, Sun Q, Gao X (June 2009). "Knockdown of p21-activated kinase 6 inhibits prostate cancer growth and enhances chemosensitivity to docetaxel". Urology. 73 (6): 1407–11. doi:10.1016/j.urology.2008.09.041. PMID19362342.
↑ Chen H, Miao J, Li H, Wang C, Li J, Zhu Y, Wang J, Wu X, Qiao H (June 2014). "Expression and prognostic significance of p21-activated kinase 6 in hepatocellular carcinoma". The Journal of Surgical Research. 189 (1): 81–8. doi:10.1016/j.jss.2014.01.049. PMID24576777.
↑ Shepelev MV, Korobko IV (January 2012). "Pak6 protein kinase is a novel effector of an atypical Rho family GTPase Chp/RhoV". Biochemistry. Biokhimiia. 77 (1): 26–32. doi:10.1134/S0006297912010038. PMID22339630. S2CID16567426.
2c30: CRYSTAL STRUCTURE OF THE HUMAN P21-ACTIVATED KINASE 6
2odb: The crystal structure of human cdc42 in complex with the CRIB domain of human p21-activated kinase 6 (PAK6)
This page is based on this Wikipedia article Text is available under the CC BY-SA 4.0 license; additional terms may apply. Images, videos and audio are available under their respective licenses.
