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]
References
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↑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 (Dec 1999). "The DNA sequence of human chromosome 22". Nature. 402 (6761): 489–95. doi:10.1038/990031. PMID10591208.
Scott RW, Olson MF (Jun 2007). "LIM kinases: function, regulation and association with human disease". Journal of Molecular Medicine. 85 (6): 555–68. doi:10.1007/s00109-007-0165-6. PMID17294230.
Osada H, Hasada K, Inazawa J, Uchida K, Ueda R, Takahashi T, Takahashi T (13 Dec 1996). "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. doi:10.1006/bbrc.1996.1847. PMID8954941.
Hiraoka J, Okano I, Higuchi O, Yang N, Mizuno K (9 Dec 1996). "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. doi:10.1016/S0014-5793(96)01303-8. PMID8980133.
Yang N, Higuchi O, Ohashi K, Nagata K, Wada A, Kangawa K, Nishida E, Mizuno K (Jun 1998). "Cofilin phosphorylation by LIM-kinase 1 and its role in Rac-mediated actin reorganization". Nature. 393 (6687): 809–12. doi:10.1038/31735. PMID9655398.
Nomoto S, Tatematsu Y, Takahashi T, Osada H (Aug 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. PMID10452946.
Sumi T, Matsumoto K, Nakamura T (Jan 2001). "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. doi:10.1074/jbc.M007074200. PMID11018042.
Sumi T, Matsumoto K, Shibuya A, Nakamura T (Jun 2001). "Activation of LIM kinases by myotonic dystrophy kinase-related Cdc42-binding kinase alpha". The Journal of Biological Chemistry. 276 (25): 23092–6. doi:10.1074/jbc.C100196200. PMID11340065.
Toshima J, Toshima JY, Takeuchi K, Mori R, Mizuno K (Aug 2001). "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. doi:10.1074/jbc.M102988200. PMID11418599.
