MEK mediates v-Src-induced disruption of the actin cytoskeleton via inactivation of the Rho-ROCK-LIM kinase pathway

Pawlak, G., Helfman, D. M. (July 2002) MEK mediates v-Src-induced disruption of the actin cytoskeleton via inactivation of the Rho-ROCK-LIM kinase pathway. Journal of Biological Chemistry, 277 (30). pp. 26927-26933. ISSN 0021-9258

URL: http://www.ncbi.nlm.nih.gov/pubmed/12011049
DOI: 10.1074/jbc.M202261200

Abstract

Cellular transformation by v-Src is believed to be caused by aberrant activation of signaling pathways that are normally regulated by cellular Src. Using normal rat kidney cells expressing a temperature-sensitive mutant of v-Src, we examined the role of the Raf/MEK/ERK, phosphatidylinositol 3-kinase/Akt, and Rho pathways in morphological transformation and cytoskeletal changes induced by v-Src. Activation of v-Src elicited a loss of actin stress fibers and focal contacts. A decrease in the phosphorylation level of cofilin was detected upon v-Src activation, which is indicative of attenuated Rho function. Inhibition of MEK using U0126 prevented v-Src-induced disruption of the cytoskeleton as well as dephosphorylation of cofilin, whereas treatment with a phosphatidylinositol 3-kinase inhibitor had no protective effect. In normal rat kidney cells stably transformed by v-Src, we found that the chronic activation of MEK induces down-regulation of ROCK expression, thereby uncoupling Rho from stress fiber formation. Taken together, these results establish MEK as an effector of v-Src-induced cytoskeleton disruption, participating in v-Src-induced antagonism of the cellular function of Rho.

Item Type: Paper
Subjects: bioinformatics > genomics and proteomics > genetics & nucleic acid processing > protein structure, function, modification > protein types > GTPase
bioinformatics > genomics and proteomics > genetics & nucleic acid processing > protein structure, function, modification
bioinformatics > genomics and proteomics > genetics & nucleic acid processing > protein structure, function, modification > protein types > actin
bioinformatics > genomics and proteomics > genetics & nucleic acid processing > protein structure, function, modification > protein types > enzymes
bioinformatics > genomics and proteomics > genetics & nucleic acid processing > protein structure, function, modification > protein types > enzymes > kinase
bioinformatics > genomics and proteomics > genetics & nucleic acid processing > protein structure, function, modification > protein types
CSHL Authors:
Communities: CSHL labs > Helfman lab
Depositing User: Matt Covey
Date: July 2002
Date Deposited: 31 Oct 2013 19:16
Last Modified: 31 Oct 2013 19:16
Related URLs:
URI: http://repository.cshl.edu/id/eprint/28764

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