LIM domain kinase 2 is an enzyme that in humans is encoded by the LIMK2 gene.[1][2][3]
There are approximately 40 known eukaryotic LIM proteins, so named for the LIM domains they contain. LIM domains are highly conserved cysteine-rich structures containing 2 zinc fingers. Although zinc fingers usually function by binding to DNA or RNA, the LIM motif probably mediates protein-protein interactions. LIM kinase-1 and LIM kinase-2 belong to a small subfamily with a unique combination of 2 N-terminal LIM motifs and a C-terminal protein kinase domain. The protein encoded by this gene is phosphorylated and activated by ROCK, a downstream effector of Rho, and the encoded protein, in turn, phosphorylates cofilin, inhibiting its actin-depolymerizing activity. It is thought that this pathway contributes to Rho-induced reorganization of the actin cytoskeleton. At least three transcript variants encoding different isoforms have been found for this gene.[3]
[edit] References
- ^ Okano I, Hiraoka J, Otera H, Nunoue K, Ohashi K, Iwashita S, Hirai M, Mizuno K (Feb 1996). "Identification and characterization of a novel family of serine/threonine kinases containing two N-terminal LIM motifs". J Biol Chem 270 (52): 31321–30. doi:10.1074/jbc.270.52.31321. PMID 8537403.
- ^ Dunham I, Shimizu N, Roe BA, Chissoe S, Hunt AR, Collins JE, Bruskiewich R, Beare DM, Clamp M, Smink LJ, Ainscough R, Almeida JP, Babbage A, Bagguley C, Bailey J, Barlow K, Bates KN, Beasley O, Bird CP, Blakey S, Bridgeman AM, Buck D, Burgess J, Burrill WD, O'Brien KP, et al. (Dec 1999). "The DNA sequence of human chromosome 22". Nature 402 (6761): 489–95. doi:10.1038/990031. PMID 10591208.
- ^ a b "Entrez Gene: LIMK2 LIM domain kinase 2". http://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=3985.
[edit] Further reading
- Scott RW, Olson MF (2007). "LIM kinases: function, regulation and association with human disease.". J. Mol. Med. 85 (6): 555–68. doi:10.1007/s00109-007-0165-6. PMID 17294230.
- Osada H, Hasada K, Inazawa J, et al. (1997). "Subcellular localization and protein interaction of the human LIMK2 gene expressing alternative transcripts with tissue-specific regulation.". Biochem. Biophys. Res. Commun. 229 (2): 582–9. doi:10.1006/bbrc.1996.1847. PMID 8954941.
- Hiraoka J, Okano I, Higuchi O, et al. (1997). "Self-association of LIM-kinase 1 mediated by the interaction between an N-terminal LIM domain and a C-terminal kinase domain.". FEBS Lett. 399 (1-2): 117–21. doi:10.1016/S0014-5793(96)01303-8. PMID 8980133.
- Yang N, Higuchi O, Ohashi K, et al. (1998). "Cofilin phosphorylation by LIM-kinase 1 and its role in Rac-mediated actin reorganization.". Nature 393 (6687): 809–12. doi:10.1038/31735. PMID 9655398.
- Nomoto S, Tatematsu Y, Takahashi T, Osada H (1999). "Cloning and characterization of the alternative promoter regions of the human LIMK2 gene responsible for alternative transcripts with tissue-specific expression.". Gene 236 (2): 259–71. doi:10.1016/S0378-1119(99)00280-2. PMID 10452946.
- Sumi T, Matsumoto K, Takai Y, Nakamura T (2000). "Cofilin phosphorylation and actin cytoskeletal dynamics regulated by rho- and Cdc42-activated LIM-kinase 2.". J. Cell Biol. 147 (7): 1519–32. doi:10.1083/jcb.147.7.1519. PMC 2174243. PMID 10613909. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=2174243.
- Sumi T, Matsumoto K, Nakamura T (2001). "Specific activation of LIM kinase 2 via phosphorylation of threonine 505 by ROCK, a Rho-dependent protein kinase.". J. Biol. Chem. 276 (1): 670–6. doi:10.1074/jbc.M007074200. PMID 11018042.
- Hartley JL, Temple GF, Brasch MA (2001). "DNA cloning using in vitro site-specific recombination.". Genome Res. 10 (11): 1788–95. doi:10.1101/gr.143000. PMC 310948. PMID 11076863. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=310948.
- Amano T, Tanabe K, Eto T, et al. (2001). "LIM-kinase 2 induces formation of stress fibres, focal adhesions and membrane blebs, dependent on its activation by Rho-associated kinase-catalysed phosphorylation at threonine-505.". Biochem. J. 354 (Pt 1): 149–59. doi:10.1042/0264-6021:3540149. PMC 1221639. PMID 11171090. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=1221639.
- Wiemann S, Weil B, Wellenreuther R, et al. (2001). "Toward a catalog of human genes and proteins: sequencing and analysis of 500 novel complete protein coding human cDNAs.". Genome Res. 11 (3): 422–35. doi:10.1101/gr.GR1547R. PMC 311072. PMID 11230166. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=311072.
- Sumi T, Matsumoto K, Shibuya A, Nakamura T (2001). "Activation of LIM kinases by myotonic dystrophy kinase-related Cdc42-binding kinase alpha.". J. Biol. Chem. 276 (25): 23092–6. doi:10.1074/jbc.C100196200. PMID 11340065.
- Toshima J, Toshima JY, Takeuchi K, et al. (2001). "Cofilin phosphorylation and actin reorganization activities of testicular protein kinase 2 and its predominant expression in testicular Sertoli cells.". J. Biol. Chem. 276 (33): 31449–58. doi:10.1074/jbc.M102988200. PMID 11418599.
- Strausberg RL, Feingold EA, Grouse LH, et al. (2003). "Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences.". Proc. Natl. Acad. Sci. U.S.A. 99 (26): 16899–903. doi:10.1073/pnas.242603899. PMC 139241. PMID 12477932. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=139241.
- Ota T, Suzuki Y, Nishikawa T, et al. (2004). "Complete sequencing and characterization of 21,243 full-length human cDNAs.". Nat. Genet. 36 (1): 40–5. doi:10.1038/ng1285. PMID 14702039.
- Colland F, Jacq X, Trouplin V, et al. (2004). "Functional proteomics mapping of a human signaling pathway.". Genome Res. 14 (7): 1324–32. doi:10.1101/gr.2334104. PMC 442148. PMID 15231748. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=442148.
- Collins JE, Wright CL, Edwards CA, et al. (2005). "A genome annotation-driven approach to cloning the human ORFeome.". Genome Biol. 5 (10): R84. doi:10.1186/gb-2004-5-10-r84. PMC 545604. PMID 15461802. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=545604.
- Wiemann S, Arlt D, Huber W, et al. (2004). "From ORFeome to biology: a functional genomics pipeline.". Genome Res. 14 (10B): 2136–44. doi:10.1101/gr.2576704. PMC 528930. PMID 15489336. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=528930.
- Vardouli L, Moustakas A, Stournaras C (2005). "LIM-kinase 2 and cofilin phosphorylation mediate actin cytoskeleton reorganization induced by transforming growth factor-beta.". J. Biol. Chem. 280 (12): 11448–57. doi:10.1074/jbc.M402651200. PMID 15647284.
[edit] External links
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PDB gallery
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1x6a: Solution structures of the second LIM domain of human LIM-kinase 2 (LIMK2)
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