Document Detail


FilGAP and its close relatives: a mediator of Rho-Rac antagonism that regulates cell morphology and migration.
MedLine Citation:
PMID:  23763313     Owner:  NLM     Status:  In-Data-Review    
Abstract/OtherAbstract:
Cell migration, phagocytosis and cytokinesis are mechanically intensive cellular processes that are mediated by the dynamic assembly and contractility of the actin cytoskeleton. GAPs (GTPase-activating proteins) control activities of the Rho family proteins including Cdc42, Rac1 and RhoA, which are prominent upstream regulators of the actin cytoskeleton. The present review concerns a class of Rho GAPs, FilGAP (ARHGAP24 gene product) and its close relatives (ARHGAP22 and AHRGAP25 gene products). FilGAP is a GAP for Rac1 and a binding partner of FLNa (filamin A), a widely expressed F-actin (filamentous actin)-cross-linking protein that binds many different proteins that are important in cell regulation. Phosphorylation of FilGAP serine/threonine residues and binding to FLNa modulate FilGAP's GAP activity and, as a result, its ability to regulate cell protrusion and spreading. FLNa binds to FilGAP at F-actin-enriched sites, such as at the leading edge of the cell where Rac1 activity is controlled to inhibit actin assembly. FilGAP then dissociates from FLNa in actin networks by myosin-dependent mechanical deformation of FLNa's FilGAP-binding site to relocate at the plasma membrane by binding to polyphosphoinositides. Since actomyosin contraction is activated downstream of RhoA-ROCK (Rho-kinase), RhoA activity regulates Rac1 through FilGAP by signalling to the force-generating system. FilGAP and the ARHGAP22 gene product also act as mediators between RhoA and Rac1 pathways, which lead to amoeboid and mesenchymal modes of cell movements respectively. Therefore FilGAP and its close relatives are key regulators that promote the reciprocal inhibitory relationship between RhoA and Rac1 in cell shape changes and the mesenchymal-amoeboid transition in tumour cells.
Authors:
Fumihiko Nakamura
Related Documents :
24153113 - Rotational positioning of nucleosomes facilitates selective binding of p53 to response ...
23641073 - Human cep192 and cep152 cooperate in plk4 recruitment and centriole duplication.
17765263 - Nucleation of an allosteric response via ligand-induced loop folding.
Publication Detail:
Type:  Journal Article    
Journal Detail:
Title:  The Biochemical journal     Volume:  453     ISSN:  1470-8728     ISO Abbreviation:  Biochem. J.     Publication Date:  2013 Jul 
Date Detail:
Created Date:  2013-06-14     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  2984726R     Medline TA:  Biochem J     Country:  England    
Other Details:
Languages:  eng     Pagination:  17-25     Citation Subset:  IM    
Affiliation:
Translational Medicine Division, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, U.S.A.
Export Citation:
APA/MLA Format     Download EndNote     Download BibTex
MeSH Terms
Descriptor/Qualifier:

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


Previous Document:  The glyoxalase pathway: the first hundred years… and beyond.
Next Document:  N-terminal tagging of two-pore channels interferes with NAADP action.