Diaphanous-related formins bridge Rho GTPase and Src tyrosine kinase signaling.
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.
Tominaga
T
T
University of California, San Francisco Cancer Center 94115, USA.
Sahai
E
E
Chardin
P
P
McCormick
F
F
Courtneidge
S A
SA
Alberts
A S
AS
D016475:3T3 Cells; D000818:Animals; D002352:Carrier Proteins / Q000378:metabolism*; D002455:Cell Division; D011992:Endosomes / Q000378:metabolism; D005326:Fetal Proteins / Q000378:metabolism*; D000080865:Formins; D020690:GTPase-Activating Proteins / Q000378:metabolism*; D005786:Gene Expression Regulation; D047908:Intracellular Signaling Peptides and Proteins; D051379:Mice; D009687:Nuclear Proteins / Q000378:metabolism*; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism; D011505:Protein-Tyrosine Kinases / Q000378:metabolism*; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D014158:Transcription, Genetic; D014162:Transfection; D054460:rho-Associated Kinases
D002352:Carrier Proteins; C491464:Diap1 protein, mouse; C120021:FHOD1 protein, human; D005326:Fetal Proteins; D000080865:Formins; D020690:GTPase-Activating Proteins; D047908:Intracellular Signaling Peptides and Proteins; D009687:Nuclear Proteins; D011993:Recombinant Fusion Proteins; C085379:rho GTPase-activating protein; D011505:Protein-Tyrosine Kinases; D017346:Protein Serine-Threonine Kinases; D054460:rho-Associated Kinases