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RhoA effector mutants reveal distinct effector pathways for cytoskeletal reorganization, SRF activation and transformation
Author(s) -
Sahai Erik,
Alberts Art S.,
Treisman Richard
Publication year - 1998
Publication title -
the embo journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 7.484
H-Index - 392
eISSN - 1460-2075
pISSN - 0261-4189
DOI - 10.1093/emboj/17.5.1350
Subject(s) - rhoa , effector , microbiology and biotechnology , biology , cytoskeleton , serum response factor , actin , transcription factor , actin cytoskeleton , small gtpase , gtpase , signal transduction , genetics , cell , gene
The RhoA GTPase regulates diverse cellular processes including cytoskeletal reorganization, transcription and transformation. Although many different potential RhoA effectors have been identified, including two families of protein kinases, their roles in RhoA‐regulated events remain unclear. We used a genetic screen to identify mutations at positions 37–42 in the RhoA effector loop that selectively disrupt effector binding, and used these to investigate the role of RhoA effectors in the formation of actin stress fibres, activation of transcription by serum response factor (SRF) and transformation. Interaction with the ROCK kinase and at least one other unidentified effector is required for stress fibre formation. Signalling to SRF by RhoA can occur in the absence of RhoA‐induced cytoskeletal changes, and did not correlate with binding to any of the effectors tested, indicating that it may be mediated by an unknown effector. Binding to ROCK‐I, but not activation of SRF, correlated with the activity of RhoA in transformation. The effector mutants should provide novel approaches for the functional study of RhoA and isolation of effector molecules involved in specific signalling processes.