G Protein-Coupled Receptors Go Extracellular: RhoA Integrates the Integrins

Integration of intracellular and extracellular signaling responses to GPCR activation. The schematic suggests mechanisms through which GPCRs may engage integrin signaling pathways and highlights a role for Cyr61/CCN1 in amplifying GPCR-mediated signals. Four possible fates are schematized for secreted Cyr61/CCN1: association with HSPGs in the ECM; association with heparin; neutralization by antibody; and association with integrins. The inset shows a theoretical time course, highlighting the Cyr61/CCN1-dependent (heparin-sensitive) contribution to intracellular signaling. The heparin-sensitive component is the difference between the green and purple lines.