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

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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.
Publisher
AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC
Issue Date
2002-07
Language
English
Article Type
Article
Keywords

SMOOTH-MUSCLE CONTRACTION; FOCAL ADHESIONS; STRESS FIBERS; PHOSPHORYLATION; TRANSFORMATION; PROTEIN; REORGANIZATION; CELLS; COFILIN; DYNAMICS

Citation

JOURNAL OF BIOLOGICAL CHEMISTRY, v.277, no.30, pp.26927 - 26933

ISSN
0021-9258
DOI
10.1074/jbc.M202261200
URI
http://hdl.handle.net/10203/81692
Appears in Collection
BS-Journal Papers(저널논문)
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