Fig. 8. Proposed signaling pathway by which R-Ras promotes strong lamellipodia formation and cell spreading. We propose that activated R-Ras directly binds to PLC at the plasma membrane and activates the integrin-PLC-Ca²⁺-signaling pathway that is required for the initiation of cell protrusion following integrin activation. The stimulation of PLC mobilizes Ca²⁺ from the endoplasmic reticulum. High cytoplasmic Ca²⁺ levels then activate Ca²⁺-dependent actin-binding proteins, such as capping proteins, causing an increase in actin polymerization. Additionally, Ca²⁺ release may also enhance the recruitment and accumulation of actin and/or adhesion components to the plasma membrane. The overall outcome is the formation of a strong ruffling lamellipod that drives leading-edge protrusion, enhancing cell spreading and adhesion.