English   español  
Please use this identifier to cite or link to this item: http://hdl.handle.net/10261/60127
Share/Impact:
Statistics
logo share SHARE logo core CORE   Add this article to your Mendeley library MendeleyBASE

Visualizar otros formatos: MARC | Dublin Core | RDF | ORE | MODS | METS | DIDL
Exportar a otros formatos:

Title

Differential involvement of H- and K-Ras in Raf-1 activation determines the role of calmodulin in MAPK signaling

AuthorsMoretó, Jemina; Santos de Dios, Eugenio
Issue Date2009
PublisherElsevier
CitationCellular Signalling 21(12): 1827-1836 (2009)
AbstractWe have previously demonstrated that inhibition of calmodulin (CaM) and the concomitant reduction of PI3K interfere with H-Ras-mediated activation of Raf-1 [1]. In the present study, we show that CaM has completely opposite effects on K-Ras-mediated Raf-1 activation. The differential contribution of CaM in the regulation of Raf-1 kinase activity via K- or H-Ras correlates with the stimulatory or inhibitory effect of CaM on MAPK phosphorylation depending on the cell type analyzed. FRET microscopy and biochemical analysis show that inhibition of CaM increases K-Ras-GTP levels and consequently its association with Raf-1. Though inhibition of CaM, using the CaM antagonist W-13, significantly increased Raf-1 activation by K-Ras-GTP, MAPK activation downstream K-Ras/Raf-1 was strongly reduced in COS-1 and several other cell lines. In contrast, in other cell lines such as NIH3T3-wt8, W-13-mediated inhibition of CaM increased Raf-1 activity, but resulted in an increase in MAPK phosphorylation. These findings suggest that modulation of K-Ras activity via CaM regulates MAPK signaling only in certain cell types. In support of this hypothesis, the comparison of H- and K-Ras expression, GTP loading and Raf-1 interaction in COS-1 and NIH3T3-wt8 suggests that the overall role of CaM in MAPK signal output is determined by the ratio of activated H- and K-Ras and the cell-specific contribution of each isoform in Raf-1 activation. © 2009 Elsevier Inc. All rights reserved.
URIhttp://hdl.handle.net/10261/60127
DOI10.1016/j.cellsig.2009.07.018
Identifiersdoi: 10.1016/j.cellsig.2009.07.018
issn: 0898-6568
Appears in Collections:(IBMCC) Artículos
Files in This Item:
File Description SizeFormat 
accesoRestringido.pdf15,38 kBAdobe PDFThumbnail
View/Open
Show full item record
Review this work
 

Related articles:


WARNING: Items in Digital.CSIC are protected by copyright, with all rights reserved, unless otherwise indicated.