LIMK1 explained

LIM domain kinase 1 is an enzyme that in humans is encoded by the LIMK1 gene.^{[1] [2]}

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, a central PDZ domain, and a C-terminal protein kinase domain. LIMK1 is likely to be a component of an intracellular signaling pathway and may be involved in brain development.

Clinical significance

LIMK1 hemizygosity is implicated in the impaired visuospatial constructive cognition of Williams syndrome.^[3]

Interactions

LIMK1 has been shown to interact with:

• CFL1,^{[4] [5]}
• CDKN1C,^[6]
• NRG1,^[7]
• PAK1,^[8]
• PAK4,^[9] and
• YWHAZ.^[10]

Further reading

• Scott RW, Olson MF . LIM kinases: function, regulation and association with human disease . J. Mol. Med. . 85 . 6 . 555–68 . 2007 . 17294230 . 10.1007/s00109-007-0165-6 . 8881246 .
• Mizuno K, Okano I, Ohashi K, Nunoue K, Kuma K, Miyata T, Nakamura T . Identification of a human cDNA encoding a novel protein kinase with two repeats of the LIM/double zinc finger motif . Oncogene . 9 . 6 . 1605–12 . 1994 . 8183554 .
• 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 . J. Biol. Chem. . 270 . 52 . 31321–30 . 1995 . 8537403 . 10.1074/jbc.270.52.31321 . free.
• Frangiskakis JM, Ewart AK, Morris CA, Mervis CB, Bertrand J, Robinson BF, Klein BP, Ensing GJ, Everett LA, Green ED, Pröschel C, Gutowski NJ, Noble M, Atkinson DL, Odelberg SJ, Keating MT . LIM-kinase1 hemizygosity implicated in impaired visuospatial constructive cognition . Cell . 86 . 1 . 59–69 . 1996 . 8689688 . 10.1016/S0092-8674(00)80077-X . 17786888 . free .
• Nebl G, Meuer SC, Samstag Y . Dephosphorylation of serine 3 regulates nuclear translocation of cofilin . J. Biol. Chem. . 271 . 42 . 26276–80 . 1996 . 8824278 . 10.1074/jbc.271.42.26276 . free.
• 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 Lett. . 399 . 1–2 . 117–21 . 1996 . 8980133 . 10.1016/S0014-5793(96)01303-8 . 2815035 . 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 . 1998 . 9655398 . 10.1038/31735 . 1998Natur.393..809Y . 4326365 .
• Wang JY, Frenzel KE, Wen D, Falls DL . Transmembrane neuregulins interact with LIM kinase 1, a cytoplasmic protein kinase implicated in development of visuospatial cognition . J. Biol. Chem. . 273 . 32 . 20525–34 . 1998 . 9685409 . 10.1074/jbc.273.32.20525 . free .
• Edwards DC, Gill GN . Structural features of LIM kinase that control effects on the actin cytoskeleton . J. Biol. Chem. . 274 . 16 . 11352–61 . 1999 . 10196227 . 10.1074/jbc.274.16.11352 . free .
• Sotiropoulos A, Gineitis D, Copeland J, Treisman R . Signal-regulated activation of serum response factor is mediated by changes in actin dynamics . Cell . 98 . 2 . 159–69 . 1999 . 10428028 . 10.1016/S0092-8674(00)81011-9 . 15781260 . free .
• Bach I, Rodriguez-Esteban C, Carrière C, Bhushan A, Krones A, Rose DW, Glass CK, Andersen B, Izpisúa Belmonte JC, Rosenfeld MG . RLIM inhibits functional activity of LIM homeodomain transcription factors via recruitment of the histone deacetylase complex . Nat. Genet. . 22 . 4 . 394–9 . 1999 . 10431247 . 10.1038/11970 . 22326394 .
• Maekawa M, Ishizaki T, Boku S, Watanabe N, Fujita A, Iwamatsu A, Obinata T, Ohashi K, Mizuno K, Narumiya S . Signaling from Rho to the actin cytoskeleton through protein kinases ROCK and LIM-kinase . Science . 285 . 5429 . 895–8 . 1999 . 10436159 . 10.1126/science.285.5429.895 .
• Edwards DC, Sanders LC, Bokoch GM, Gill GN . Activation of LIM-kinase by Pak1 couples Rac/Cdc42 GTPase signalling to actin cytoskeletal dynamics . Nat. Cell Biol. . 1 . 5 . 253–9 . 1999 . 10559936 . 10.1038/12963 . 25250183 .
• Ohashi K, Nagata K, Maekawa M, Ishizaki T, Narumiya S, Mizuno K . Rho-associated kinase ROCK activates LIM-kinase 1 by phosphorylation at threonine 508 within the activation loop . J. Biol. Chem. . 275 . 5 . 3577–82 . 2000 . 10652353 . 10.1074/jbc.275.5.3577 . free .
• Martindale DW, Wilson MD, Wang D, Burke RD, Chen X, Duronio V, Koop BF . Comparative genomic sequence analysis of the Williams syndrome region (LIMK1-RFC2) of human chromosome 7q11.23 . Mamm. Genome . 11 . 10 . 890–8 . 2000 . 11003705 . 10.1007/s003350010166 . 8575994 .
• Sumi T, Matsumoto K, Shibuya A, Nakamura T . Activation of LIM kinases by myotonic dystrophy kinase-related Cdc42-binding kinase alpha . J. Biol. Chem. . 276 . 25 . 23092–6 . 2001 . 11340065 . 10.1074/jbc.C100196200 . free .
• Dan C, Kelly A, Bernard O, Minden A . Cytoskeletal changes regulated by the PAK4 serine/threonine kinase are mediated by LIM kinase 1 and cofilin . J. Biol. Chem. . 276 . 34 . 32115–21 . 2001 . 11413130 . 10.1074/jbc.M100871200 . 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 . J. Biol. Chem. . 276 . 33 . 31449–58 . 2001 . 11418599 . 10.1074/jbc.M102988200 . free.

External links

• LIMK1 Info with links in the Cell Migration Gateway

Notes and References

1. Tassabehji M, Metcalfe K, Fergusson WD, Carette MJ, Dore JK, Donnai D, Read AP, Pröschel C, Gutowski NJ, Mao X, Sheer D . LIM-kinase deleted in Williams syndrome . Nat. Genet. . 13 . 3 . 272–3 . Aug 1996 . 8673124 . 10.1038/ng0796-272 . 138698 .
2. Osborne LR, Martindale D, Scherer SW, Shi XM, Huizenga J, Heng HH, Costa T, Pober B, Lew L, Brinkman J, Rommens J, Koop B, Tsui LC . Identification of genes from a 500-kb region at 7q11.23 that is commonly deleted in Williams syndrome patients . Genomics . 36 . 2 . 328–36 . Jan 1997 . 8812460 . 10.1006/geno.1996.0469 . free .
3. Web site: Entrez Gene: LIMK1 LIM domain kinase 1.
4. Foletta VC, Lim MA, Soosairajah J, Kelly AP, Stanley EG, Shannon M, He W, Das S, Massague J, Bernard O, Soosairaiah J . Direct signaling by the BMP type II receptor via the cytoskeletal regulator LIMK1 . J. Cell Biol. . 162 . 6 . 1089–98 . September 2003 . 12963706 . 2172847 . 10.1083/jcb.200212060 .
5. Maekawa M, Ishizaki T, Boku S, Watanabe N, Fujita A, Iwamatsu A, Obinata T, Ohashi K, Mizuno K, Narumiya S . Signaling from Rho to the actin cytoskeleton through protein kinases ROCK and LIM-kinase . Science . 285 . 5429 . 895–8 . August 1999 . 10436159 . 10.1126/science.285.5429.895 .
6. Yokoo T, Toyoshima H, Miura M, Wang Y, Iida KT, Suzuki H, Sone H, Shimano H, Gotoda T, Nishimori S, Tanaka K, Yamada N . p57Kip2 regulates actin dynamics by binding and translocating LIM-kinase 1 to the nucleus . J. Biol. Chem. . 278 . 52 . 52919–23 . December 2003 . 14530263 . 10.1074/jbc.M309334200 . free .
7. Wang JY, Frenzel KE, Wen D, Falls DL . Transmembrane neuregulins interact with LIM kinase 1, a cytoplasmic protein kinase implicated in development of visuospatial cognition . J. Biol. Chem. . 273 . 32 . 20525–34 . August 1998 . 9685409 . 10.1074/jbc.273.32.20525 . free .
8. Edwards DC, Sanders LC, Bokoch GM, Gill GN . Activation of LIM-kinase by Pak1 couples Rac/Cdc42 GTPase signalling to actin cytoskeletal dynamics . Nat. Cell Biol. . 1 . 5 . 253–9 . September 1999 . 10559936 . 10.1038/12963 . 25250183 .
9. Dan C, Kelly A, Bernard O, Minden A . Cytoskeletal changes regulated by the PAK4 serine/threonine kinase are mediated by LIM kinase 1 and cofilin . J. Biol. Chem. . 276 . 34 . 32115–21 . August 2001 . 11413130 . 10.1074/jbc.M100871200 . free .
10. Birkenfeld J, Betz H, Roth D . Identification of cofilin and LIM-domain-containing protein kinase 1 as novel interaction partners of 14-3-3 zeta . Biochem. J. . 369 . Pt 1 . 45–54 . January 2003 . 12323073 . 1223062 . 10.1042/BJ20021152 .