LIM kinase and Diaphanous cooperate to regulate serum response factor and actin dynamics.
The small GTPase RhoA controls activity of serum response factor (SRF) by inducing changes in actin dynamics. We show that in PC12 cells, activation of SRF after serum stimulation is RhoA dependent, requiring both actin polymerization and the Rho kinase (ROCK)-LIM kinase (LIMK)-cofilin signaling pathway, previously shown to control F-actin turnover. Activation of SRF by overexpression of wild-type LIMK or ROCK-insensitive LIMK mutants also requires functional RhoA, indicating that a second RhoA-dependent signal is involved. This is provided by the RhoA effector mDia: dominant interfering mDia1 derivatives inhibit both serum- and LIMK-induced SRF activation and reduce the ability of LIMK to induce F-actin accumulation. These results demonstrate a role for LIMK in SRF activation, and functional cooperation between RhoA-controlled LIMK and mDia effector pathways.
Geneste
Olivier
O
Cancer Research UK London Research Institute, Lincoln's Inn Fields Laboratories, WC2A 3PX, UK.
Copeland
John W
JW
Treisman
Richard
R
D051339:Actin Depolymerizing Factors; D000199:Actins / Q000378:metabolism*; D000818:Animals; D002352:Carrier Proteins / Q000378:metabolism*; D047908:Intracellular Signaling Peptides and Proteins; D054461:Lim Kinases; D008840:Microfilament Proteins / Q000378:metabolism; D009474:Neurons / Q000166:cytology / Q000201:enzymology*; D016716:PC12 Cells; D010766:Phosphorylation; D011494:Protein Kinases / Q000378:metabolism*; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism; D051381:Rats; D026362:Serum Response Factor / Q000378:metabolism*; D054460:rho-Associated Kinases; D020742:rhoA GTP-Binding Protein / Q000378:metabolism
D051339:Actin Depolymerizing Factors; D000199:Actins; D002352:Carrier Proteins; D047908:Intracellular Signaling Peptides and Proteins; D008840:Microfilament Proteins; D026362:Serum Response Factor; D011494:Protein Kinases; D054461:Lim Kinases; C515894:Limk1 protein, rat; D017346:Protein Serine-Threonine Kinases; D054460:rho-Associated Kinases; D020742:rhoA GTP-Binding Protein