Disease relevance of Limk1

• We resolve this paradox by showing that the effects of LIMK1 expression on migration, intravasation, and metastasis of cancer cells can be most simply explained by its regulation of the output of the cofilin pathway [1].
• Genetic studies have implicated a mutation of LIMK1 as a causative factor in the impairment of visuospatial cognition in a neurodevelopmental disorder, Williams syndrome [2].

High impact information on Limk1

• Phosphorylation by LIM-kinase 1 inactivates cofilin, leading to accumulation of actin filaments [3].
• Regulation of actin dynamics through phosphorylation of cofilin by LIM-kinase [3].
• Cofilin, a LIMK1 substrate, is essential for the regulation of actin polymerization and depolymerization during cell migration [1].
• In addition, we also found that LIMK1 activation occurs through Rac/Cdc42- and p21-activated kinase-mediated signaling pathways [2].
• LIM kinase 1 (LIMK1), a novel member of a subclass of the protein-serine/threonine kinases, is known to play a role in the development and maintenance of neuronal circuits that mediate cognitive function [2].

Biological context of Limk1

• In this study, the effect of LIMK1 overexpression in PC12 cell apoptosis was investigated [4].
• LIMK-1 and LIMK-2 mRNAs mostly co-localized during development and are expressed preferentially in the central nervous system during mid-to-late gestation but the signals decreased during the post-natal period [5].
• We previously isolated two novel serine/threonine kinase genes containing the LIM motif (LIMK-1 and LIMK-2) from a rat cDNA library [5].
• However, differential gene expression was observed in some nuclei in the CNS; LIMK-1 mRNA was intensely expressed in the facial motor nucleus, the hypoglossal nucleus, deep nuclei of the cerebellum and the layers 3, 5 and 6 of the adult cerebral cortex while only LIMK-2 mRNA was preferentially expressed in the some parts of the epithelium [5].
• Comparison of tissue distribution of two novel serine/threonine kinase genes containing the LIM motif (LIMK-1 and LIMK-2) in the developing rat [5].

Anatomical context of Limk1

• The inhibition of JNK activation was observed in the PC12 cells overexpressing the wild-type LIMK1 after serum withdrawal [4].
• In the nasal cavity, LIMK-1 and LIMK-2 mRNAs were expressed complementarily [5].
• The long-term overexpression of LIMK1 produces growth cone collapse and axon retraction, an effect that is dependent on its growth cone localization [6].
• LIM kinase 1 activates cAMP-responsive element-binding protein during the neuronal differentiation of immortalized hippocampal progenitor cells [2].
• LIM kinase 1 accumulates in presynaptic terminals during synapse maturation [7].

Associations of Limk1 with chemical compounds

• In summary, this report illustrates that Sertoli germ cell AJ dynamics are regulated, at least in part, via the integrin/ROCK/LIMK/cofilin signaling pathway [8].
• Identification of the LIM kinase-1 as a ceramide-regulated gene in renal mesangial cells [9].
• Dual regulation of LIM kinase 1 expression by cyclic AMP and calcium determines cofilin phosphorylation states during neuritogenesis in NG108-15 cells [10].
• Mechanistically, the ceramide-induced LIMK-1 expression is blocked by the Rho kinase inhibitor Y27632, but not by a farnesyl transferase inhibitor, suggesting the involvement of the small G protein Rho, but not Ras and Rac, in the expressional upregulation [9].

Regulatory relationships of Limk1

• PC12 cells overexpressing the wild-type LIMK1 were more resistant to serum-withdrawal-induced cell death and the level of caspase 3 activation in these cells was lower than in the control PC12 cells or than in the PC12 cells expressing a mutant LIMK1 lacking the kinase domain [4].
• Similar to exogenously added ceramide, also interleukin-1beta which is an established activator of the neutral sphingomyelinase that leads to endogenous ceramide formation upregulates LIMK-1 protein expression and activity [9].

Other interactions of Limk1

• Northern blot analysis revealed the expression of LIMK-1 mRNA predominantly in the brain and the expression of LIMK-2 mRNA in various tissues in the rat [11].
• Exposure of neurons to extracellular stimuli such as brain-derived neurotrophic factor relieves miR-134 inhibition of Limk1 translation and in this way may contribute to synaptic development, maturation and/or plasticity [12].
• Overexpression of LIM kinase 1 renders resistance to apoptosis in PC12 cells by inhibition of caspase activation [4].
• Confocal microscopy, subcellular fractionation, and expression of several epitope-tagged LIMK1 constructs revealed that LIMK1 is enriched in the Golgi apparatus and growth cones, with the LIM domain required for Golgi localization and the PDZ domain for its presence at neuritic tips [6].

Analytical, diagnostic and therapeutic context of Limk1

• Immunoprecipitation and immunoblots revealed that the induction of LIMK1 was mediated via an increase in its phospho-Ser but not phospho-Tyr content [8].

References