title: Rac, membrane heterogeneity, caveolin and regulation of growth by integrins.
abstract: Anchorage dependence of growth blocks cell proliferation in inappropriate environments, thereby inhibiting cancer cell invasion and metastasis. Inhibition of growth regulatory pathways, including Rac, Erk and PtdIns 3-kinase in non-adherent cells mediates this effect. Here, we review recent work showing that integrin-mediated adhesion controls Rac binding to membranes. Rac binding sites can be found within cholesterol-enriched membrane domains, which are internalized when cells are deprived of adhesion. Endocytosis of these domains is mediated by caveolae and regulated by caveolin-1 phosphorylated on Tyr 14. This mechanism can account for the control of multiple pathways by integrins, thus providing an important mechanism for anchorage dependence of growth.
authors.affiliation: Integrin Signalling Laboratory, Centro Nacional de Investigaciones Cardiovasculares, Melchor Fernández Almagro 3, Madrid, Spain.
authors.forename: Miguel A
authors.initials: MA
authors.lastname: Del Pozo
authors.forename: Martin A
authors.initials: MA
authors.lastname: Schwartz
mesh_terms: D000818:Animals; D022461:Caveolins / Q000502:physiology*; D002448:Cell Adhesion; D002462:Cell Membrane / Q000502:physiology*; D049109:Cell Proliferation; D006801:Humans; D016023:Integrins / Q000502:physiology*; D020744:rac GTP-Binding Proteins / Q000502:physiology*
chemical_list: D022461:Caveolins; D016023:Integrins; D020744:rac GTP-Binding Proteins