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.
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.
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.
PAK3 is overexpressed in neuroendocrine/carcinoids tumors. PAK3 has been shown to be important for synapse formation and plasticity, and contribute to mental retardation. Further, a point mutation in PAK3 gene has been associated with nonsyndromic X-linked mental retardation.
^Knaus UG, Morris S, Dong HJ, Chernoff J, Bokoch GM (July 1995). "Regulation of human leukocyte p21-activated kinases through G protein--coupled receptors". Science. 269 (5221): 221–3. doi:10.1126/science.7618083. PMID7618083.
^Manser E, Chong C, Zhao ZS, Leung T, Michael G, Hall C, Lim L (October 1995). "Molecular cloning of a new member of the p21-Cdc42/Rac-activated kinase (PAK) family". The Journal of Biological Chemistry. 270 (42): 25070–8. doi:10.1074/jbc.270.42.25070. PMID7559638.
^ abBagrodia S, Taylor SJ, Creasy CL, Chernoff J, Cerione RA (September 1995). "Identification of a mouse p21Cdc42/Rac activated kinase". The Journal of Biological Chemistry. 270 (39): 22731–7. doi:10.1074/jbc.270.39.22731. PMID7559398.
^ abBurbelo PD, Kozak CA, Finegold AA, Hall A, Pirone DM (May 1999). "Cloning, central nervous system expression and chromosomal mapping of the mouse PAK-1 and PAK-3 genes". Gene. 232 (2): 209–15. doi:10.1016/s0378-1119(99)00110-9. PMID10352232.
^ abBoda B, Alberi S, Nikonenko I, Node-Langlois R, Jourdain P, Moosmayer M, Parisi-Jourdain L, Muller D (December 2004). "The mental retardation protein PAK3 contributes to synapse formation and plasticity in hippocampus". The Journal of Neuroscience. 24 (48): 10816–25. doi:10.1523/jneurosci.2931-04.2004. PMID15574732.
^Kreis P, Rousseau V, Thévenot E, Combeau G, Barnier JV (August 2008). "The four mammalian splice variants encoded by the p21-activated kinase 3 gene have different biological properties". Journal of Neurochemistry. 106 (3): 1184–97. doi:10.1111/j.1471-4159.2008.05474.x. PMID18507705.
^Bagrodia S, Bailey D, Lenard Z, Hart M, Guan JL, Premont RT, Taylor SJ, Cerione RA (August 1999). "A tyrosine-phosphorylated protein that binds to an important regulatory region on the cool family of p21-activated kinase-binding proteins". The Journal of Biological Chemistry. 274 (32): 22393–400. doi:10.1074/jbc.274.32.22393. PMID10428811.
^ abBagrodia S, Taylor SJ, Jordon KA, Van Aelst L, Cerione RA (September 1998). "A novel regulator of p21-activated kinases". The Journal of Biological Chemistry. 273 (37): 23633–6. doi:10.1074/jbc.273.37.23633. PMID9726964.
^Liu RX, Wang WQ, Ye L, Bi YF, Fang H, Cui B, Zhou WW, Dai M, Zhang J, Li XY, Ning G (August 2010). "p21-activated kinase 3 is overexpressed in thymic neuroendocrine tumors (carcinoids) with ectopic ACTH syndrome and participates in cell migration". Endocrine. 38 (1): 38–47. doi:10.1007/s12020-010-9324-6. PMID20960100.