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LIM domain kinase 2

LIMK2, LIM-kinase 2, Limk2b, Limk2a
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. [provided by RefSeq, Jul 2008] (from NCBI)
Top mentioned proteins: LIM, LIMK1, Actin, cofilin, Rhodopsin
Papers using LIMK2 antibodies
BMP-2 decreases Mash1 stability by increasing Id1 expression.
Supplier
Henrique Domingos, In PLoS ONE, 2003
... (Amersham); p38α, p38δ, Phospho-p38 MAP Kinase (Thr180/Tyr182), MAPKAP-2, Phospho-MAPKAP-2 (Thr222), Phospho-Hsp27 (Ser15), LIMK1 and Phospho-LIMK1 (Thr508)/LIMK2(Thr505) (Cell Signaling, Beverly, MA) ...
Endosomes generate localized Rho–ROCK–MLC2–based contractile signals via Endo180 to promote adhesion disassembly
Supplier
Isacke Clare M. et al., In The Journal of Cell Biology, 2000
... Rabbit anti–human monophospho-MLC2 (Ser19) and diphospho-MLC2 (Thr18/Ser19), LIMK1, and phospho-LIMK1 (Thr508)/LIMK2 (Thr505) were obtained from Cell Signaling.
p160ROCK, a Rho-associated coiled-coil forming protein kinase, works downstream of Rho and induces focal adhesions
Supplier
Arkowitz Robert Alan, In PLoS ONE, 1996
... Recombinant Myosin Light Chain and LIMK2 were from Calbiochem and Life Technologies, respectively ...
Papers on LIMK2
Roles of LIM kinases in central nervous system function and dysfunction.
Review
New
Bénédetti et al., Orléans, France. In Febs Lett, Jan 2016
LIM kinase 1 (LIMK1) and LIM kinase 2 (LIMK2) regulate actin dynamics by phosphorylating cofilin.
Whole exome sequencing identifies rare protein-coding variants in Behçet's disease.
New
Sawalha et al., Ann Arbor, United States. In Arthritis Rheumatol, Jan 2016
We detected genetic association between BD and LIMK2 (rs149034313), involved in regulating cytoskeletal reorganization, and NEIL1 (rs5745908), involved in base excision DNA repair (P=3.22x10(-4) and P=5.16x10(-4) , respectively).
Altered Expression of CDC42 Signaling Pathway Components in Cortical Layer 3 Pyramidal Cells in Schizophrenia.
New
Lewis et al., Pittsburgh, United States. In Biol Psychiatry, Jan 2016
RESULTS: Relative to comparison subjects, CDC42EP4, LIMK1, LIMK2, ARHGDIA, and PAK3 messenger RNA levels were significantly upregulated in subjects with schizophrenia in laminar and cellular samples.
LIM kinase inhibitors disrupt mitotic microtubule organization and impair tumor cell proliferation.
New
Olson et al., London, United Kingdom. In Oncotarget, Dec 2015
These findings encouraged a drug discovery effort that led to development of CRT0105446 and CRT0105950, which potently block LIMK1 and LIMK2 activity in vitro, and inhibit cofilin phosphorylation and increase αTubulin acetylation in cells.
Discovery, Development, and SAR of Aminothiazoles as LIMK Inhibitors with Cellular Anti-Invasive Properties.
New
Olson et al., Glasgow, United Kingdom. In J Med Chem, Nov 2015
Scaffold hopping and subsequent SAR directed development led to a series of low nanomolar inhibitors of LIMK1 and LIMK2 that also inhibited the direct biomarker p-cofilin in cells and inhibited the invasion of MDA MB-231-luc cells in a matrigel inverse invasion assay.
Design, synthesis and biological characterization of selective LIMK inhibitors.
New
Defert et al., Diepenbeek, Belgium. In Bioorg Med Chem Lett, Oct 2015
Exploration of structure-activity relationships revealed that many of such compounds, including LX-7101, cause potent inhibition of LIMK1 and LIMK2, and also ROCK2 and PKA.
Involvement of Rho-Kinase/LIM Kinase/Cofilin Signaling Pathway in Corporal Fibrosis after Cavernous Nerve Injury in Male Rats.
New
Cho et al., Seoul, South Korea. In J Sex Med, Jul 2015
AIM: To determine whether the LIMK2/cofilin pathway, the downstream effectors of ROCK1, was involved in ED and corporal fibrosis following bilateral CN injury in male rats.
Actin remodelling factors control ciliogenesis by regulating YAP/TAZ activity and vesicle trafficking.
Kim et al., Taejŏn, South Korea. In Nat Commun, 2014
We also identify actin remodelling factors LIMK2 and TESK1 as key players in the ciliogenesis control network in which YAP/TAZ and directional vesicle trafficking are integral components.
Neurofibromin - protein structure and cellular functions in the context of neurofibromatosis type I pathogenesis.
Review
Gos et al., Warsaw, Poland. In Postepy Hig Med Dosw (online), 2014
Neurofibromin also interacts with many other proteins that are engaged in intracellular transport (tubulin, kinesin), actin cytoskeleton rearrangements (LIMK2, Rho and Rac) or morphogenesis of neural cells (syndecans, CRMP proteins).
Endothelin-1 induces LIMK2-mediated programmed necrotic neuronal death independent of NOS activity.
Kang et al., South Korea. In Mol Brain, 2014
BACKGROUND: Recently, we have reported that LIM kinase 2 (LIMK2) involves programmed necrotic neuronal deaths induced by aberrant cyclin D1 expression following status epilepticus (SE).
Kinome-wide functional analysis highlights the role of cytoskeletal remodeling in somatic cell reprogramming.
Impact
Rana et al., Los Angeles, United States. In Cell Stem Cell, 2014
We found that shRNA-mediated knockdown of the serine/threonine kinases TESK1 or LIMK2 promoted mesenchymal-to-epithelial transition, decreased COFILIN phosphorylation, and disrupted Actin filament structures during reprogramming of mouse embryonic fibroblasts.
[LIM kinases and their roles in the nervous system].
Review
Zhang et al., Hangzhou, China. In Zhejiang Da Xue Xue Bao Yi Xue Ban, 2014
LIM kinase-1 (LIMK1) and LIM kinase-2 (LIMK2) are kinases that have serine/threonine and tyrosine dual specificity.
Novel LIMK2 Inhibitor Blocks Panc-1 Tumor Growth in a mouse xenograft model.
Kloog et al., Tel Aviv-Yafo, Israel. In Oncoscience, 2013
The LIMK family consists of two homologues, LIMK1 and LIMK2, which differ from one another in expression profile, intercellular localization, and function.
LIM kinases are attractive targets with many macromolecular partners and only a few small molecule regulators.
Review
Manetti, Siena, Italy. In Med Res Rev, 2012
The LIM kinases 1 and 2 (LIMK1 and LIMK2) are dual specificity (serine/threonine and tyrosine) kinases.
LIMK2d, a truncated isoform of Lim kinase 2 regulates neurite growth in absence of the LIM kinase domain.
GeneRIF
Andres et al., Tours, France. In Biochem Biophys Res Commun, 2012
these results indicate that LIMK2d is a third LIMK2 isoform which regulates neurite extension and highlights the possible existence of a kinase independent function of LIMK2.
LIMK2 is a crucial regulator and effector of Aurora-A-kinase-mediated malignancy.
GeneRIF
Shah et al., West Lafayette, United States. In J Cell Sci, 2012
LIMK2 positively regulates the level of Aurora A, thereby engaging in a positive-feedback loop, promoting Aurora-A-mediated oncogenic pathways.
p53-mediated transcriptional regulation and activation of the actin cytoskeleton regulatory RhoC to LIMK2 signaling pathway promotes cell survival.
GeneRIF
Olson et al., Glasgow, United Kingdom. In Cell Res, 2011
LIMK2 variant isoforms were found to be regulated by p53 through direct interaction with regulatory elements within the LIMK2 gene.
p53-Mediated transactivation of LIMK2b links actin dynamics to cell cycle checkpoint control.
GeneRIF
Shieh et al., Taipei, Taiwan. In Oncogene, 2010
a novel pathway whereby LIMK2b, acting downstream of p53, ensures proper execution of checkpoint arrest by modulating the dynamics of actin polymerization
[Effects of LIMK2 RNA interference on the mechanosensitivity of c-fos gene in osteoblast].
GeneRIF
Fu et al., Guangzhou, China. In Zhonghua Yi Xue Za Zhi, 2010
Using RNAi against LIMK2 to inhibit the cytoskeleton reorganization can promote the expression of c-fos gene and thus enhance the mechanosensitivity of c-fos gene in osteoblasts.
PDZ and LIM domain-encoding genes: molecular interactions and their role in development.
Review
Bagowski et al., Leiden, Netherlands. In Scientificworldjournal, 2006
In mammals, there are ten genes that encode for both a PDZ domain, and one or several LIM domains: four genes of the ALP subfamily (ALP, Elfin, Mystique, and RIL), three of the Enigma subfamily (Enigma, Enigma Homolog, and ZASP), the two LIM kinases (LIMK1 and LIMK2), and the LIM only protein 7 (LMO7).
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