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LIMK2-1, a new isoform of human LIMK2, regulates actin cytoskeleton remodeling via a different signaling pathway than that of its two homologs, LIMK2a and LIMK2b
- Source :
- The Biochemical journal. 475(23)
- Publication Year :
- 2017
-
Abstract
- LIMK1 and LIMK2 (LIMKs, LIM kinases) are kinases that play a crucial role in cytoskeleton dynamics by independently regulating both actin filament and microtubule remodeling. LIMK1 and, more recently, LIMK2 have been shown to be involved in cancer development and metastasis, resistance of cancer cells to microtubule-targeted treatments, neurological diseases, and viral infection. LIMKs have thus recently emerged as new therapeutic targets. Databanks describe three isoforms of human LIMK2: LIMK2a, LIMK2b, and LIMK2-1. Evidence suggests that they may not have completely overlapping functions. We biochemically characterized the three isoforms to better delineate their potential roles, focusing on LIMK2-1, which has only been described at the mRNA level in a single study. LIMK2-1 has a protein phosphatase 1 (PP1) inhibitory domain at its C-terminus which its two counterparts do not. We showed that the LIMK2-1 protein is indeed synthesized. LIMK2-1 does not phosphorylate cofilin, the canonical substrate of LIMKs, although it has kinase activity and promotes actin stress fiber formation. Instead, it interacts with PP1 and partially inhibits its activity towards cofilin. Our data suggest that LIMK2-1 regulates actin cytoskeleton dynamics by preventing PP1-mediated cofilin dephosphorylation, rather than by directly phosphorylating cofilin as its two counterparts, LIMK2a and LIMK2b. This specificity may allow for tight regulation of the phospho-cofilin pool, determining the fate of the cell.
- Subjects :
- 0301 basic medicine
Cytoplasm
Stress fiber
macromolecular substances
LIMK1
environment and public health
Biochemistry
03 medical and health sciences
Protein Phosphatase 1
Humans
Amino Acid Sequence
Kinase activity
Phosphorylation
Cytoskeleton
Molecular Biology
Actin
Cell Nucleus
Sequence Homology, Amino Acid
Kinase
Chemistry
Lim Kinases
Cell Biology
Cofilin
Actin cytoskeleton
Cell biology
Isoenzymes
Actin Cytoskeleton
030104 developmental biology
HEK293 Cells
Actin Depolymerizing Factors
RNA Interference
HeLa Cells
Signal Transduction
Subjects
Details
- ISSN :
- 14708728
- Volume :
- 475
- Issue :
- 23
- Database :
- OpenAIRE
- Journal :
- The Biochemical journal
- Accession number :
- edsair.doi.dedup.....05af57157866ce49c21d6c4fae542911