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.
Muller
S M
SM
School of Biomedical Sciences, Queen's Medical Centre, Nottingham, NG7 2UH, United Kingdom.
Okan
E
E
Jones
P
P
D016475:3T3 Cells; D000818:Animals; D002448:Cell Adhesion; D005786:Gene Expression Regulation; D006801:Humans; D051379:Mice; D016297:Mutagenesis, Site-Directed; D011956:Receptors, Cell Surface / Q000235:genetics*; D055293:Receptors, Urokinase Plasminogen Activator; D011994:Recombinant Proteins / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014158:Transcription, Genetic; D014162:Transfection; D020764:cdc42 GTP-Binding Protein / Q000378:metabolism*; D020830:rac1 GTP-Binding Protein / Q000378:metabolism*; D018631:ras Proteins / Q000378:metabolism*; D020742:rhoA GTP-Binding Protein / Q000378:metabolism*
C524898:PLAUR protein, human; C524899:Plaur protein, mouse; D011956:Receptors, Cell Surface; D055293:Receptors, Urokinase Plasminogen Activator; D011994:Recombinant Proteins; D020764:cdc42 GTP-Binding Protein; D020830:rac1 GTP-Binding Protein; D018631:ras Proteins; D020742:rhoA GTP-Binding Protein