Disease relevance of LIMK2

• When expressed in HeLa cells, wild-type LIMK2, but not the T505V mutant, induced the formation of stress fibres, focal adhesions and membrane blebs [1].
• Along with the development of rat pulmonary artery and right ventricular hypertrophy, monocrotaline treatment also induced the mRNA and protein contents of profilin, cofilin-2 and LIMK2 in PASMCs [2].
• In this study, we have determined the effect of ribozymes specific for LIM kinase-2 on metastatic and proliferative phenotypes of human fibrosarcoma cells [3].
• The LIMK-2 transcript was also induced upon neuroectodermal differentiation of mouse P19 embryonal carcinoma cells [4].
• LIMK-2 is related to the neuronally expressed LIM-kinase, whose hemizygous deletion appears to result in cognitive impairment in patients with Williams syndrome [4].

High impact information on LIMK2

• Par-3 binds to LIMK2 but not to the related kinase LIMK1 [5].
• Par-3 inhibits LIMK2 activity in vitro, and overexpressed Par-3 suppresses cofilin phosphorylation that is induced by lysophosphatidic acid [5].
• In contrast, the coexpression of LIMK2/KD with the activated Rac did not affect Rac-induced lamellipodia formation [6].
• Cofilin phosphorylation and actin cytoskeletal dynamics regulated by rho- and Cdc42-activated LIM-kinase 2 [6].
• LIMK2 is expressed in the epidermal basal layer and signals downstream of the GTPase Rac1 to promote extracellular matrix adhesion and inhibit terminal differentiation [7].

Biological context of LIMK2

• These results indicate that ROCK directly phosphorylates threonine 505 and activates LIMK2 downstream of RhoA and that this phosphorylation is essential for LIMK2 to induce actin cytoskeletal reorganization [8].
• Our study shows that phorbol ester and serum stimulation of endothelial cells inhibit nuclear import of LIMK2 but not LIMK1 [9].
• Cloning and characterization of the alternative promoter regions of the human LIMK2 gene responsible for alternative transcripts with tissue-specific expression [10].
• Mutagenesis studies showed that phosphorylation of Thr-494, a putative protein kinase C phosphorylation site identified within the nuclear localization signal, inhibits nuclear import of the enhanced green fluorescent protein-PDZ kinase domain of LIMK2 [11].
• The activity of LIMK2, distinct from LIMK1, toward cofilin phosphorylation did not change in the normal cell division cycle [12].

Anatomical context of LIMK2

• Furthermore, inhibitors of Rho and ROCK significantly suppressed LIMK2-induced stress fibres and membrane blebs [1].
• Immunoblotting and immunoprecipitation analyses of mouse tissues and human and mouse cell lines revealed widespread expression of the 75-kDa LIMK2 protein [13].
• Immunohistochemical studies revealed that LIMK2 is widely expressed in embryonic and adult mouse tissues and that its expression pattern is similar to that of LIMK1 except in the testes [13].
• Inhibition of nuclear import of LIMK2 in endothelial cells by protein kinase C-dependent phosphorylation at Ser-283 [9].
• The Myc epitope-tagged LIMK1 and LIMK2 proteins transiently expressed in COS cells exhibited serine/threonine-specific kinase activity toward myelin basic protein and histone in in vitro kinase assay [14].

Associations of LIMK2 with chemical compounds

• ROCK directly phosphorylated the threonine 505 residue within the activation segment of LIMK2 and markedly stimulated LIMK2 activity [8].
• Using immunofluorescence monitoring of enhanced green fluorescent protein-tagged LIMK2 in combination with photobleaching techniques and leptomycin B treatment, we demonstrate that LIMK2 shuttles between the cytoplasm and the nucleus in endothelial cells [9].
• In contrast, LIMK2 was hyperphosphorylated and its activity was markedly increased when HeLa cells were synchronized at mitosis with nocodazole treatment [12].
• Phosphorylated LIM kinase 2 and cofilin, related to actin bundling and integrin clustering, were dephosphorylated (activated) by Y-27632 [15].
• At the subcellular level, LIMK-2 is localized in both the nucleus and in a Triton X-100 soluble fraction [4].

Regulatory relationships of LIMK2

• Par-3 mediates the inhibition of LIM kinase 2 to regulate cofilin phosphorylation and tight junction assembly [5].

Other interactions of LIMK2

• To examine this differential tissue-specific expression in detail, an RNase protection assay was performed, which demonstrated three expression patterns of the LIMK2 isoforms [10].

Analytical, diagnostic and therapeutic context of LIMK2

• Immunofluorescence and subcellular fractionation analysis revealed that Myc-tagged LIMK1 and LIMK2 were localized mainly in the cytoplasm [14].
• Sequence analysis predicted two PKC phosphorylation sites in LIMK2 but not in LIMK1 [9].
• Chromosomal localization of human LIMK1 and LIMK2 genes was assigned to 7q11.23 and 22q12, respectively, by fluorescence in situ hybridization [14].
• Through site-directed mutagenesis, we identified the basic amino acid-rich motif KKRTLRKNDRKKR (amino acids 491-503) as the functional nuclear and nucleolar localization signal of LIMK2 [11].

References