LIM kinases: function, regulation and association with human disease

@article{Scott2007LIMKF,
  title={LIM kinases: function, regulation and association with human disease},
  author={Rebecca W. Scott and Michael F. Olson},
  journal={Journal of Molecular Medicine},
  year={2007},
  volume={85},
  pages={555-568}
}
  • R. Scott, M. Olson
  • Published 10 February 2007
  • Biology
  • Journal of Molecular Medicine
The LIM kinase family consists of just two members: LIM kinase 1 (LIMK1) and LIM kinase 2 (LIMK2). With uniquely organised signalling domains, LIM kinases are regulated by several upstream signalling pathways, principally acting downstream of Rho GTPases to influence the architecture of the actin cytoskeleton by regulating the activity of the cofilin family proteins cofilin1, cofilin2 and destrin. Although the LIM kinases are very homologous, particularly when comparing kinase domains, there is… 

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TLDR
The present review describes the LIMK conformational space and its dependence on ligand binding and explains the unique catalytic mechanism of the kinase, shedding light on substrate recognition and how LIMK activity is regulated.
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References

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TLDR
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, and it was demonstrated that endogenous LimK1 and LimK2 form heterodimers, and thatLimK2 does not always interact with the same proteins as LIMK 1.
The N-terminal LIM domain negatively regulates the kinase activity of LIM-kinase 1.
TLDR
Results suggest that the N-terminal LIM domain negatively regulates the kinase activity of LIMK1 by direct interaction with the C-Terminal kinase domain.
The N-terminal LIM domain negatively regulates the kinase activity of LIM-kinase 1.
TLDR
Results suggest that the N-terminal LIM domain negatively regulates the kinase activity of LIMK1 by direct interaction with the C-Terminal kinase domain.
Hsp90 increases LIM kinase activity by promoting its homo‐dimerization
TLDR
It is shown that the half‐life of LIMK1 in cells depends on the presence of active Hsp90, and these findings implicate HSp90 in the stabilization of LimK1 by promoting homodimer formation and transphosphorylation.
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TLDR
Evidence is reported that LIMK1 and LIMK2 activities toward cofilin phosphorylation are stimulated in cells by the co-expression of myotonic dystrophy kinase-related Cdc42-binding kinase α (MRCKα), an effector protein kinase of CDC42.
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TLDR
Results suggest that the PDZ domain, particularly the B region, of LIMK1 has a specific function to localize the protein in the cytoplasm, and probably has nuclear export signal activity.
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TLDR
Results indicate phosphorylation is an essential regulatory feature of LIM kinase and indicate that threonine 508 and the adjacent basic insert sequences of the activation loop are required for this process.
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TLDR
It is proposed thatXLIMK is a putative regulator of cytoskeletal rearrangements during oocyte maturation, and the interaction between XLIMK activity and microtubule dynamics seems highly likely.
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TLDR
It is demonstrated that GST-Limk1-fusion protein can autophosphorylate on serine, tyrosine and threonine residues in vitro and that mutation of residue D460 within the IHRDL motif abolishes kinase activity.
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