LIMK2 explained

LIM domain kinase 2 is an enzyme that in humans is encoded by the LIMK2 gene.^{[1] [2] [3]}

Function

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.

Further reading

• Scott RW, Olson MF . LIM kinases: function, regulation and association with human disease . Journal of Molecular Medicine . 85 . 6 . 555–68 . Jun 2007 . 17294230 . 10.1007/s00109-007-0165-6 . 8881246 .
• Osada H, Hasada K, Inazawa J, Uchida K, Ueda R, Takahashi T, Takahashi T . Subcellular localization and protein interaction of the human LIMK2 gene expressing alternative transcripts with tissue-specific regulation . Biochemical and Biophysical Research Communications . 229 . 2 . 582–9 . 13 Dec 1996 . 8954941 . 10.1006/bbrc.1996.1847 .
• Hiraoka J, Okano I, Higuchi O, Yang N, Mizuno K . Self-association of LIM-kinase 1 mediated by the interaction between an N-terminal LIM domain and a C-terminal kinase domain . FEBS Letters . 399 . 1–2 . 117–21 . 9 Dec 1996 . 8980133 . 10.1016/S0014-5793(96)01303-8 . free .
• Yang N, Higuchi O, Ohashi K, Nagata K, Wada A, Kangawa K, Nishida E, Mizuno K . Cofilin phosphorylation by LIM-kinase 1 and its role in Rac-mediated actin reorganization . Nature . 393 . 6687 . 809–12 . Jun 1998 . 9655398 . 10.1038/31735 . 1998Natur.393..809Y . 4326365 .
• Nomoto S, Tatematsu Y, Takahashi T, Osada H . 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 . Aug 1999 . 10452946 . 10.1016/S0378-1119(99)00280-2 .
• Sumi T, Matsumoto K, Takai Y, Nakamura T . Cofilin phosphorylation and actin cytoskeletal dynamics regulated by rho- and Cdc42-activated LIM-kinase 2 . The Journal of Cell Biology . 147 . 7 . 1519–32 . 27 Dec 1999 . 10613909 . 2174243 . 10.1083/jcb.147.7.1519 .
• Sumi T, Matsumoto K, Nakamura T . Specific activation of LIM kinase 2 via phosphorylation of threonine 505 by ROCK, a Rho-dependent protein kinase . The Journal of Biological Chemistry . 276 . 1 . 670–6 . Jan 2001 . 11018042 . 10.1074/jbc.M007074200 . free .
• Hartley JL, Temple GF, Brasch MA . DNA cloning using in vitro site-specific recombination . Genome Research . 10 . 11 . 1788–95 . Nov 2000 . 11076863 . 310948 . 10.1101/gr.143000 .
• Amano T, Tanabe K, Eto T, Narumiya S, Mizuno K . 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 . The Biochemical Journal . 354 . Pt 1 . 149–59 . Feb 2001 . 11171090 . 1221639 . 10.1042/0264-6021:3540149 .
• Wiemann S, Weil B, Wellenreuther R, Gassenhuber J, Glassl S, Ansorge W, Böcher M, Blöcker H, Bauersachs S, Blum H, Lauber J, Düsterhöft A, Beyer A, Köhrer K, Strack N, Mewes HW, Ottenwälder B, Obermaier B, Tampe J, Heubner D, Wambutt R, Korn B, Klein M, Poustka A . Toward a catalog of human genes and proteins: sequencing and analysis of 500 novel complete protein coding human cDNAs . Genome Research . 11 . 3 . 422–35 . Mar 2001 . 11230166 . 311072 . 10.1101/gr.GR1547R .
• Sumi T, Matsumoto K, Shibuya A, Nakamura T . Activation of LIM kinases by myotonic dystrophy kinase-related Cdc42-binding kinase alpha . The Journal of Biological Chemistry . 276 . 25 . 23092–6 . Jun 2001 . 11340065 . 10.1074/jbc.C100196200 . free .
• Toshima J, Toshima JY, Takeuchi K, Mori R, Mizuno K . Cofilin phosphorylation and actin reorganization activities of testicular protein kinase 2 and its predominant expression in testicular Sertoli cells . The Journal of Biological Chemistry . 276 . 33 . 31449–58 . Aug 2001 . 11418599 . 10.1074/jbc.M102988200 . free .
• Colland F, Jacq X, Trouplin V, Mougin C, Groizeleau C, Hamburger A, Meil A, Wojcik J, Legrain P, Gauthier JM . Functional proteomics mapping of a human signaling pathway . Genome Research . 14 . 7 . 1324–32 . Jul 2004 . 15231748 . 442148 . 10.1101/gr.2334104 .
• Collins JE, Wright CL, Edwards CA, Davis MP, Grinham JA, Cole CG, Goward ME, Aguado B, Mallya M, Mokrab Y, Huckle EJ, Beare DM, Dunham I . A genome annotation-driven approach to cloning the human ORFeome . Genome Biology . 5 . 10 . R84 . 2005 . 15461802 . 545604 . 10.1186/gb-2004-5-10-r84 . free .
• Wiemann S, Arlt D, Huber W, Wellenreuther R, Schleeger S, Mehrle A, Bechtel S, Sauermann M, Korf U, Pepperkok R, Sültmann H, Poustka A . From ORFeome to biology: a functional genomics pipeline . Genome Research . 14 . 10B . 2136–44 . Oct 2004 . 15489336 . 528930 . 10.1101/gr.2576704 .
• Vardouli L, Moustakas A, Stournaras C . LIM-kinase 2 and cofilin phosphorylation mediate actin cytoskeleton reorganization induced by transforming growth factor-beta . The Journal of Biological Chemistry . 280 . 12 . 11448–57 . Mar 2005 . 15647284 . 10.1074/jbc.M402651200 . free .

External links

• LIMK2 Info with links in the Cell Migration Gateway

Notes and References

1. Okano I, Hiraoka J, Otera H, Nunoue K, Ohashi K, Iwashita S, Hirai M, Mizuno K . Identification and characterization of a novel family of serine/threonine kinases containing two N-terminal LIM motifs . The Journal of Biological Chemistry . 270 . 52 . 31321–30 . Dec 1995 . 8537403 . 10.1074/jbc.270.52.31321 . free .
2. 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 . The DNA sequence of human chromosome 22 . Nature . 402 . 6761 . 489–95 . Dec 1999 . 10591208 . 10.1038/990031 . 1999Natur.402..489D . free .
3. Web site: Entrez Gene: LIMK2 LIM domain kinase 2.