EVIDENCE FOR INVOLVEMENT OF PHOSPHOLIPASE C-GAMMA-2 IN SIGNAL TRANSDUCTION OF PLATELET-DERIVED GROWTH-FACTOR IN VASCULAR SMOOTH-MUSCLE CELLS

In order to examine the mechanisms underlying smooth-muscle cell proliferation, we investigated effect of platelet-derived growth factor (PDGF) dimers on proliferation of rabbit vascular smooth-muscle cells (VSMCs) and also involvement of phospholipase C (PLC) isoforms in the signal transduction. PDGF-BB and -AB, but not -AA, stimulated cell proliferation and intracellular production of inositol trisphosphate. Northern and Western analyses demonstrated that VSMCs mainly expressed PLC-gamma2 and PLC-delta1 among four PLC isoforms tested. A number of cellular proteins, including PLC-gamma2, but not PLC-delta1, were phosphorylated on a tyrosine residue by the stimulation of either PDGF-BB or -AB. These results suggest a functional association of PDGF receptor and PLC-gamma2 that might be responsible for PDGF-dependent VSMC growth. In addition, the expression of PLC-gamma2 was extremely low in the primary VSMC cultures and was induced during further cultivation of the primary cultures, indicating that an acquisition of PDGF-signal-transducing components, including PLC-gamma2, may be an important step for proliferation of smooth-muscle cells.