Regulation of urokinase receptor transcription by Ras- and Rho-family GTPases.

How cell adhesion is coordinated with extracellular proteolysis is a key question in understanding cell migration. Potentially, the small GTP-binding proteins that affect actin organisation and signal transduction may also regulate the expression of genes associated with extracellular proteolysis. We investigated the ability of Ras, Rac-1, Cdc42Hs, and RhoA to regulate transcription from the1.55-kb promoter region of the human urokinase plasminogen activator receptor (uPAR) gene. Constitutively active V12 H-Ras and Rho-A stimulated uPAR transcription while Cdc42Hs and Rac-1 did not. The use of Ras effector-loop mutants indicated that signalling via multiple Ras-effectors is necessary for the maximum activation of transcription. Copyright 2000 Academic Press.