LIM domain kinase 1

Details

Name
LIM domain kinase 1
Synonyms
  • 2.7.11.1
  • LIMK
  • LIMK-1
Gene Name
LIMK1
Organism
Humans
Amino acid sequence
>lcl|BSEQ0008608|LIM domain kinase 1
MRLTLLCCTWREERMGEEGSELPVCASCGQRIYDGQYLQALNADWHADCFRCCDCSASLS
HQYYEKDGQLFCKKDYWARYGESCHGCSEQITKGLVMVAGELKYHPECFICLTCGTFIGD
GDTYTLVEHSKLYCGHCYYQTVVTPVIEQILPDSPGSHLPHTVTLVSIPASSHGKRGLSV
SIDPPHGPPGCGTEHSHTVRVQGVDPGCMSPDVKNSIHVGDRILEINGTPIRNVPLDEID
LLIQETSRLLQLTLEHDPHDTLGHGLGPETSPLSSPAYTPSGEAGSSARQKPVLRSCSID
RSPGAGSLGSPASQRKDLGRSESLRVVCRPHRIFRPSDLIHGEVLGKGCFGQAIKVTHRE
TGEVMVMKELIRFDEETQRTFLKEVKVMRCLEHPNVLKFIGVLYKDKRLNFITEYIKGGT
LRGIIKSMDSQYPWSQRVSFAKDIASGMAYLHSMNIIHRDLNSHNCLVRENKNVVVADFG
LARLMVDEKTQPEGLRSLKKPDRKKRYTVVGNPYWMAPEMINGRSYDEKVDVFSFGIVLC
EIIGRVNADPDYLPRTMDFGLNVRGFLDRYCPPNCPPSFFPITVRCCDLDPEKRPSFVKL
EHWLETLRMHLAGHLPLGPQLEQLDRGFWETYRRGESGLPAHPEVPD
Number of residues
647
Molecular Weight
72584.4
Theoretical pI
Not Available
GO Classification
Functions
ATP binding / heat shock protein binding / protein kinase activity / protein serine/threonine kinase activity / zinc ion binding
Processes
actin cytoskeleton organization / axon guidance / ephrin receptor signaling pathway / Fc-gamma receptor signaling pathway involved in phagocytosis / innate immune response / negative regulation of ubiquitin-protein transferase activity / nervous system development / positive regulation of actin filament bundle assembly / positive regulation of axon extension / positive regulation of stress fiber assembly / protein phosphorylation / Rho protein signal transduction / signal transduction / small GTPase mediated signal transduction
Components
cytoplasm / cytosol / focal adhesion / membrane / neuron projection / nucleoplasm
General Function
Zinc ion binding
Specific Function
Serine/threonine-protein kinase that plays an essential role in the regulation of actin filament dynamics. Acts downstream of several Rho family GTPase signal transduction pathways. Activated by upstream kinases including ROCK1, PAK1 and PAK4, which phosphorylate LIMK1 on a threonine residue located in its activation loop. LIMK1 subsequently phosphorylates and inactivates the actin binding/depolymerizing factors cofilin-1/CFL1, cofilin-2/CFL2 and destrin/DSTN, thereby preventing the cleavage of filamentous actin (F-actin), and stabilizing the actin cytoskeleton. In this way LIMK1 regulates several actin-dependent biological processes including cell motility, cell cycle progression, and differentiation. Phosphorylates TPPP on serine residues, thereby promoting microtubule disassembly. Stimulates axonal outgrowth and may be involved in brain development. Isoform 3 has a dominant negative effect on actin cytoskeletal changes. Required for atypical chemokine receptor ACKR2-induced phosphorylation of cofilin (CFL1).
Pfam Domain Function
Transmembrane Regions
Not Available
Cellular Location
Cytoplasm
Gene sequence
>lcl|BSEQ0013301|LIM domain kinase 1 (LIMK1)
ATGCTGTTGGCTTCAGCCCCAAGAAGACGCCGCTTCCTCCAGAGGGCTAAGTGTTGTGAC
TGCAGTGCCTCCCTGTCGCACCAGTACTATGAGAAGGATGGGCAGCTCTTCTGCAAGAAG
GACTACTGGGCCCGCTATGGCGAGTCCTGCCATGGGTGCTCTGAGCAAATCACCAAGGGA
CTGGTTATGGTGGCTGGGGAGCTGAAGTACCACCCCGAGTGTTTCATCTGCCTCACGTGT
GGGACCTTTATCGGTGACGGGGACACCTACACGCTGGTGGAGCACTCCAAGCTGTACTGC
GGGCACTGCTACTACCAGACTGTGGTGACCCCCGTCATCGAGCAGATCCTGCCTGACTCC
CCTGGCTCCCACCTGCCCCACACCGTCACCCTGGTGTCCATCCCAGCCTCATCTCATGGC
AAGCGTGGACTTTCAGTCTCCATTGACCCCCCGCACGGCCCACCGGGCTGTGGCACCGAG
CACTCACACACCGTCCGCGTCCAGGGAGTGGATCCGGGCTGCATGAGCCCAGATGTGAAG
AATTCCATCCACGTCGGAGACCGGATCTTGGAAATCAATGGCACGCCCATCCGAAATGTG
CCCCTGGACGAGATTGACCTGCTGATTCAGGAAACCAGCCGCCTGCTCCAGCTGACCCTC
GAGCATGACCCTCACGATACACTGGGCCACGGGCTGGGGCCTGAGACCAGCCCCCTGAGC
TCTCCGGCTTATACTCCCAGCGGGGAGGCGGGCAGCTCTGCCCGGCAGAAACCTGTCTTG
AGGAGCTGCAGCATCGACAGGTCTCCGGGCGCTGGCTCACTGGGCTCCCCGGCCTCCCAG
CGCAAGGACCTGGGTCGCTCTGAGTCCCTCCGCGTAGTCTGCCGGCCACACCGCATCTTC
CGGCCGTCGGACCTCATCCACGGGGAGGTGCTGGGCAAGGGCTGCTTCGGCCAGGCTATC
AAGGTGACACACCGTGAGACAGGTGAGGTGATGGTGATGAAGGAGCTGATCCGGTTCGAC
GAGGAGACCCAGAGGACGTTCCTCAAGGAGGTGAAGGTCATGCGATGCCTGGAACACCCC
AACGTGCTCAAGTTCATCGGGGTGCTCTACAAGGACAAGAGGCTCAACTTCATCACTGAG
TACATCAAGGGCGGCACGCTCCGGGGCATCATCAAGAGCATGGACAGCCAGTACCCATGG
AGCCAGAGAGTGAGCTTTGCCAAGGACATCGCATCAGGGATGGCCTACCTCCACTCCATG
AACATCATCCACCGAGACCTCAACTCCCACAACTGCCTGGTCCGCGAGAACAAGAATGTG
GTGGTGGCTGACTTCGGGCTGGCGCGTCTCATGGTGGACGAGAAGACTCAGCCTGAGGGC
CTGCGGAGCCTCAAGAAGCCAGACCGCAAGAAGCGCTACACCGTGGTGGGCAACCCCTAC
TGGATGGCACCTGAGATGATCAACGGCCGCAGCTATGATGAGAAGGTGGATGTGTTCTCC
TTTGGGATCGTCCTGTGCGAGATCATCGGGCGGGTGAACGCAGACCCTGACTACCTGCCC
CGCACCATGGACTTTGGCCTCAACGTGCGAGGATTCCTGGACCGCTACTGCCCCCCAAAC
TGCCCCCCGAGCTTCTTCCCCATCACCGTGCGCTGTTGCGATCTGGACCCCGAGAAGAGG
CCATCCTTTGTGAAGCTGGAACACTGGCTGGAGACCCTCCGCATGCACCTGGCCGGCCAC
CTGCCACTGGGCCCACAGCTGGAGCAGCTGGACAGAGGTTTCTGGGAGACCTACCGGCGC
GGCGAGAGCGGACTGCCTGCCCACCCTGAGGTCCCCGACTGA
Chromosome Location
7
Locus
Not Available
External Identifiers
ResourceLink
UniProtKB IDP53667
UniProtKB Entry NameLIMK1_HUMAN
HGNC IDHGNC:6613
General References
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  2. Frangiskakis JM, Ewart AK, Morris CA, Mervis CB, Bertrand J, Robinson BF, Klein BP, Ensing GJ, Everett LA, Green ED, Proschel C, Gutowski NJ, Noble M, Atkinson DL, Odelberg SJ, Keating MT: LIM-kinase1 hemizygosity implicated in impaired visuospatial constructive cognition. Cell. 1996 Jul 12;86(1):59-69. [PubMed:8689688]
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  7. 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. 1999 Sep;1(5):253-9. [PubMed:10559936]
  8. 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. 1999 Aug 6;285(5429):895-8. [PubMed:10436159]
  9. 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. 2000 Feb 4;275(5):3577-82. [PubMed:10652353]
  10. Sumi T, Matsumoto K, Shibuya A, Nakamura T: Activation of LIM kinases by myotonic dystrophy kinase-related Cdc42-binding kinase alpha. J Biol Chem. 2001 Jun 22;276(25):23092-6. Epub 2001 May 4. [PubMed:11340065]
  11. 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. 2001 Aug 24;276(34):32115-21. Epub 2001 Jun 18. [PubMed:11413130]
  12. Niwa R, Nagata-Ohashi K, Takeichi M, Mizuno K, Uemura T: Control of actin reorganization by Slingshot, a family of phosphatases that dephosphorylate ADF/cofilin. Cell. 2002 Jan 25;108(2):233-46. [PubMed:11832213]
  13. Kaji N, Ohashi K, Shuin M, Niwa R, Uemura T, Mizuno K: Cell cycle-associated changes in Slingshot phosphatase activity and roles in cytokinesis in animal cells. J Biol Chem. 2003 Aug 29;278(35):33450-5. Epub 2003 Jun 14. [PubMed:12807904]
  14. 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. 2003 Dec 26;278(52):52919-23. Epub 2003 Oct 6. [PubMed:14530263]
  15. Hillman RT, Green RE, Brenner SE: An unappreciated role for RNA surveillance. Genome Biol. 2004;5(2):R8. Epub 2004 Feb 2. [PubMed:14759258]
  16. Soosairajah J, Maiti S, Wiggan O, Sarmiere P, Moussi N, Sarcevic B, Sampath R, Bamburg JR, Bernard O: Interplay between components of a novel LIM kinase-slingshot phosphatase complex regulates cofilin. EMBO J. 2005 Feb 9;24(3):473-86. Epub 2005 Jan 20. [PubMed:15660133]
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  18. Kobayashi M, Nishita M, Mishima T, Ohashi K, Mizuno K: MAPKAPK-2-mediated LIM-kinase activation is critical for VEGF-induced actin remodeling and cell migration. EMBO J. 2006 Feb 22;25(4):713-26. Epub 2006 Feb 2. [PubMed:16456544]
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  20. Acevedo K, Li R, Soo P, Suryadinata R, Sarcevic B, Valova VA, Graham ME, Robinson PJ, Bernard O: The phosphorylation of p25/TPPP by LIM kinase 1 inhibits its ability to assemble microtubules. Exp Cell Res. 2007 Dec 10;313(20):4091-106. [PubMed:18028908]
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Drug Relations

Drug Relations
DrugBank IDNameDrug groupPharmacological action?ActionsDetails
DB08912Dabrafenibapproved, investigationalunknownantagonistinhibitorDetails
DB12010Fostamatinibapproved, investigationalunknowninhibitorDetails