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Papers In Press, published online ahead of print May 7, 2001
Transcription Laboratory, Imperial Cancer Research Fund Laboratories, London WC2A 3PX
Corresponding Author: R.Treisman{at}icrf.icnet.uk
Activation of the transcription factor SRF is dependent on Rho-controlled changes in actin dynamics. We used pathway-specific inhibitors to compare the roles of actin dynamics, MEK-ERK signalling, and Phosphatidylinositol 3-kinase (PI-3K) in signalling either to SRF itself or to four cellular SRF target genes. Serum, LPA, PDGF and the phorbol ester TPA each activated transcription of a stably integrated SRF reporter gene, dependent on functional RhoA GTPase. Inhibition of MEK reduced activation of the SRF reporter by all stimuli by about 50%, except for TPA, which was effectively blocked. Inhibition of PI-3K slightly reduced reporter activation by serum and LPA, but substantially inhibited activation by PDGF and TPA. Reporter induction by all stimuli was absolutely dependent on actin dynamics. Regulation of the SRF (srf) and vinculin (vcl) genes was similar to that of the SRF reporter gene: activation by all stimuli was Rho-dependent and required actin dynamics, but was largely independent of MEK activity. In contrast, activation of fos and egr1 occured independently of RhoA and actin polymerisation, but was almost completely dependent on MEK activation. These results show that at least two classes of SRF target genes can be distinguished on the basis of their relative sensitivity to RhoA-actin and MEK-ERK signalling pathways.
J. Biol. Chem, 10.1074/jbc.M102678200
Submitted on March 26, 2001
Revised on April 27, 2001
Accepted on May 6, 2001
Differential usage of signal transduction pathways defines two types of SRF target gene
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