TY - JOUR
T1 - Diaphanous-related formins bridge Rho GTPase and Src tyrosine kinase signaling
AU - Tominaga, Tomoko
AU - Sahai, Erik
AU - Chardin, Pierre
AU - McCormick, Frank
AU - Courtneidge, Sara A.
AU - Alberts, Arthur S.
N1 - Funding Information:
We thank David Stokoe, Luika Timmerman, Matija Peterlin, and other members of the UCSF Cancer Research Institute for discussions and comments on the manuscript. We also thank Dr. C. Lowell for Src −/− Yes −/− fibroblasts, Dr. Suzanne Pfeffer for the transferrin receptor antibodies and Dr. H. Kawakatsu for active Src mAb 28. A.S.A. thanks Richard Treisman for supporting the initial stages of this work and S. Olatunde for technical assistance. We also thank Drs. S. Narumiya, T. Ishizaki, and N. Watanabe for mDia1 and ROCK constructs; M. Broome for Src expression plasmids; and Drs. S. Suetsugu and T. Takenawa for profilin plasmids. Funding to A.S.A was provided by the Carol Franc Buck Fellowship and F.M., the David A. Wood Endowment. P.C. was supported by the Lincy Foundation at the UCSF CRI.
PY - 2000/1
Y1 - 2000/1
N2 - We have examined the role of the mouse Diaphanous-related formin (DRF) Rho GTPase binding proteins, mDia1 and mDia2, in cell regulation. The DRFs are required for cytokinesis, stress fiber formation, and transcriptional activation of the serum response factor (SRF). 'Activated' mDia1 and mDia2 variants, lacking their GTPase binding domains, cooperated with Rho-kinase or ROCK to form stress fibers but independently activated SRF. Src tyrosine kinase associated and co-localized with the DRFs in endosomes and in mid-bodies of dividing cells. Inhibition of Src also blocked cytokinesis, SRF induction by activated DRFs, and cooperative stress fiber formation with active ROCK. Our results show that the DRF proteins couple Rho and Src during signaling and the regulation of actin dynamics.
AB - We have examined the role of the mouse Diaphanous-related formin (DRF) Rho GTPase binding proteins, mDia1 and mDia2, in cell regulation. The DRFs are required for cytokinesis, stress fiber formation, and transcriptional activation of the serum response factor (SRF). 'Activated' mDia1 and mDia2 variants, lacking their GTPase binding domains, cooperated with Rho-kinase or ROCK to form stress fibers but independently activated SRF. Src tyrosine kinase associated and co-localized with the DRFs in endosomes and in mid-bodies of dividing cells. Inhibition of Src also blocked cytokinesis, SRF induction by activated DRFs, and cooperative stress fiber formation with active ROCK. Our results show that the DRF proteins couple Rho and Src during signaling and the regulation of actin dynamics.
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U2 - 10.1016/S1097-2765(00)80399-8
DO - 10.1016/S1097-2765(00)80399-8
M3 - Article
C2 - 10678165
AN - SCOPUS:0012644537
SN - 1097-2765
VL - 5
SP - 13
EP - 25
JO - Molecular Cell
JF - Molecular Cell
IS - 1
ER -