Beta-arrestins operate an on/off control switch for focal adhesion kinase activity.

Focal adhesion kinase (FAK) regulates key biological processes downstream of G protein-coupled receptors (GPCRs) in normal and cancer cells, but the modes of kinase activation by these receptors remain unclear. We report that after GPCR stimulation, FAK activation is controlled by a sequence of events depending on the scaffolding proteins β-arrestins and G proteins. Depletion of β-arrestins results in a marked increase in FAK autophosphorylation and focal adhesion number.

Methods to Characterize Protein Interactions with β-Arrestin In Cellulo.

β-Arrestins 1 and 2 (β-arr1 and β-arr2) are ubiquitous proteins with common and distinct functions. They were initially identified as proteins recruited to stimulated G protein-coupled receptors (GPCRs), regulating their desensitization and internalization. The discovery that β-arrs could also interact with more than 400 non-GPCR protein partners brought to light their central roles as multifunctional scaffold proteins regulating multiple signalling pathways from the plasma membrane to the nucleus, downstream of GPCRs or independently from these receptors.

VEGF-induced endothelial cell migration requires urokinase receptor (uPAR)-dependent integrin redistribution.

Aims: Vascular endothelial growth factor (VEGF)-initiated angiogenesis requires coordinated proteolytic degradation of extracellular matrix provided by the urokinase plasminogen activator/urokinase receptor (uPA/uPAR) system and regulation of cell migration provided by integrin-matrix interaction. In this study, we investigated the mechanisms underlying the uPAR-dependent modulation of VEGF-induced endothelial migration.

Methods And Results: We used flow cytometry to quantify integrins at the cell surface.