LIMK1

LIM domain kinase 1
Available structures PDB Ortholog search: PDBe, RCSB List of PDB id codes 3S95​
Identifiers
Symbols	LIMK1 ; LIMK; LIMK-1
External IDs	OMIM: 601329 MGI: 104572 HomoloGene: 1738 ChEMBL: 3836 GeneCards: LIMK1 Gene
EC number	2.7.11.1
Gene ontology Molecular function • protein kinase activity • protein serine/threonine kinase activity • protein binding • ATP binding • zinc ion binding • heat shock protein binding • protein heterodimerization activity Cellular component • nucleoplasm • cytoplasm • cytosol • focal adhesion • membrane • neuron projection Biological process • protein phosphorylation • signal transduction • small GTPase mediated signal transduction • Rho protein signal transduction • nervous system development • axon guidance • actin cytoskeleton organization • positive regulation of actin filament bundle assembly • Fc-gamma receptor signaling pathway involved in phagocytosis • innate immune response • positive regulation of axon extension • ephrin receptor signaling pathway • negative regulation of ubiquitin-protein transferase activity • positive regulation of stress fiber assembly Sources: Amigo / QuickGO
RNA expression pattern
More reference expression data
Orthologs
Species	Human	Mouse
Entrez	3984	16885
Ensembl	ENSG00000106683	ENSMUSG00000029674
UniProt	P53667	P53668
RefSeq (mRNA)	NM_001204426	NM_001305875
RefSeq (protein)	NP_001191355	NP_001292804
Location (UCSC)	Chr 7: 74.08 – 74.12 Mb	Chr 5: 134.66 – 134.69 Mb
PubMed search

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.^[3]

Clinical signficance

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]

References

1. Tassabehji M, Metcalfe K, Fergusson WD, Carette MJ, Dore JK, Donnai D, Read AP, Pröschel C, Gutowski NJ, Mao X, Sheer D (Aug 1996). "LIM-kinase deleted in Williams syndrome". Nat. Genet. 13 (3): 272–3. doi:10.1038/ng0796-272. PMID 8673124.
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 (Jan 1997). "Identification of genes from a 500-kb region at 7q11.23 that is commonly deleted in Williams syndrome patients". Genomics 36 (2): 328–36. doi:10.1006/geno.1996.0469. PMID 8812460.
3. "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 (September 2003). "Direct signaling by the BMP type II receptor via the cytoskeletal regulator LIMK1". J. Cell Biol. 162 (6): 1089–98. doi:10.1083/jcb.200212060. PMC 2172847. PMID 12963706.
5. Maekawa M, Ishizaki T, Boku S, Watanabe N, Fujita A, Iwamatsu A, Obinata T, Ohashi K, Mizuno K, Narumiya S (August 1999). "Signaling from Rho to the actin cytoskeleton through protein kinases ROCK and LIM-kinase". Science 285 (5429): 895–8. doi:10.1126/science.285.5429.895. PMID 10436159.
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 (December 2003). "p57Kip2 regulates actin dynamics by binding and translocating LIM-kinase 1 to the nucleus". J. Biol. Chem. 278 (52): 52919–23. doi:10.1074/jbc.M309334200. PMID 14530263.
7. Wang JY, Frenzel KE, Wen D, Falls DL (August 1998). "Transmembrane neuregulins interact with LIM kinase 1, a cytoplasmic protein kinase implicated in development of visuospatial cognition". J. Biol. Chem. 273 (32): 20525–34. doi:10.1074/jbc.273.32.20525. PMID 9685409.
8. Edwards DC, Sanders LC, Bokoch GM, Gill GN (September 1999). "Activation of LIM-kinase by Pak1 couples Rac/Cdc42 GTPase signalling to actin cytoskeletal dynamics". Nat. Cell Biol. 1 (5): 253–9. doi:10.1038/12963. PMID 10559936.
9. Dan C, Kelly A, Bernard O, Minden A (August 2001). "Cytoskeletal changes regulated by the PAK4 serine/threonine kinase are mediated by LIM kinase 1 and cofilin". J. Biol. Chem. 276 (34): 32115–21. doi:10.1074/jbc.M100871200. PMID 11413130.
10. Birkenfeld J, Betz H, Roth D (January 2003). "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. doi:10.1042/BJ20021152. PMC 1223062. PMID 12323073.

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.
• Mizuno K, Okano I, Ohashi K, Nunoue K, Kuma K, Miyata T, Nakamura T (1994). "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. PMID 8183554.
• Okano I, Hiraoka J, Otera H, Nunoue K, Ohashi K, Iwashita S, Hirai M, Mizuno K (1995). "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.
• 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 (1996). "LIM-kinase1 hemizygosity implicated in impaired visuospatial constructive cognition". Cell 86 (1): 59–69. doi:10.1016/S0092-8674(00)80077-X. PMID 8689688.
• Nebl G, Meuer SC, Samstag Y (1996). "Dephosphorylation of serine 3 regulates nuclear translocation of cofilin". J. Biol. Chem. 271 (42): 26276–80. doi:10.1074/jbc.271.42.26276. PMID 8824278.
• Hiraoka J, Okano I, Higuchi O, Yang N, Mizuno K (1996). "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, Nagata K, Wada A, Kangawa K, Nishida E, Mizuno K (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.
• Wang JY, Frenzel KE, Wen D, Falls DL (1998). "Transmembrane neuregulins interact with LIM kinase 1, a cytoplasmic protein kinase implicated in development of visuospatial cognition". J. Biol. Chem. 273 (32): 20525–34. doi:10.1074/jbc.273.32.20525. PMID 9685409.
• Edwards DC, Gill GN (1999). "Structural features of LIM kinase that control effects on the actin cytoskeleton". J. Biol. Chem. 274 (16): 11352–61. doi:10.1074/jbc.274.16.11352. PMID 10196227.
• Sotiropoulos A, Gineitis D, Copeland J, Treisman R (1999). "Signal-regulated activation of serum response factor is mediated by changes in actin dynamics". Cell 98 (2): 159–69. doi:10.1016/S0092-8674(00)81011-9. PMID 10428028.
• Bach I, Rodriguez-Esteban C, Carrière C, Bhushan A, Krones A, Rose DW, Glass CK, Andersen B, Izpisúa Belmonte JC, Rosenfeld MG (1999). "RLIM inhibits functional activity of LIM homeodomain transcription factors via recruitment of the histone deacetylase complex". Nat. Genet. 22 (4): 394–9. doi:10.1038/11970. PMID 10431247.
• Maekawa M, Ishizaki T, Boku S, Watanabe N, Fujita A, Iwamatsu A, Obinata T, Ohashi K, Mizuno K, Narumiya S (1999). "Signaling from Rho to the actin cytoskeleton through protein kinases ROCK and LIM-kinase". Science 285 (5429): 895–8. doi:10.1126/science.285.5429.895. PMID 10436159.
• Edwards DC, Sanders LC, Bokoch GM, Gill GN (1999). "Activation of LIM-kinase by Pak1 couples Rac/Cdc42 GTPase signalling to actin cytoskeletal dynamics". Nat. Cell Biol. 1 (5): 253–9. doi:10.1038/12963. PMID 10559936.
• Ohashi K, Nagata K, Maekawa M, Ishizaki T, Narumiya S, Mizuno K (2000). "Rho-associated kinase ROCK activates LIM-kinase 1 by phosphorylation at threonine 508 within the activation loop". J. Biol. Chem. 275 (5): 3577–82. doi:10.1074/jbc.275.5.3577. PMID 10652353.
• Martindale DW, Wilson MD, Wang D, Burke RD, Chen X, Duronio V, Koop BF (2000). "Comparative genomic sequence analysis of the Williams syndrome region (LIMK1-RFC2) of human chromosome 7q11.23". Mamm. Genome 11 (10): 890–8. doi:10.1007/s003350010166. PMID 11003705.
• 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.
• Dan C, Kelly A, Bernard O, Minden A (2001). "Cytoskeletal changes regulated by the PAK4 serine/threonine kinase are mediated by LIM kinase 1 and cofilin". J. Biol. Chem. 276 (34): 32115–21. doi:10.1074/jbc.M100871200. PMID 11413130.
• Toshima J, Toshima JY, Takeuchi K, Mori R, Mizuno K (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.

External links

• LIMK1 Info with links in the Cell Migration Gateway