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-gamma 2 and PLC-delta 1 among four PLC isoforms tested. A number of cellular proteins, including PLC-gamma 2, but not PLC-delta 1, 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-gamma 2 that might be responsible for PDGF-dependent VSMC growth. In addition, the expression of PLC-gamma 2 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-gamma 2, may be an important step for proliferation of smooth-muscle cells.
Homma
Y
Y
Department of Biosignal Research, Tokyo Metropolitan Institute of Gerontology, Japan.
Sakamoto
H
H
Tsunoda
M
M
Aoki
M
M
Takenawa
T
T
Ooyama
T
T
D000818:Animals; D015152:Blotting, Northern; D015153:Blotting, Western; D002455:Cell Division; D002478:Cells, Cultured; D015870:Gene Expression; D007163:Immunosorbent Techniques; D046911:Macromolecular Substances; D009131:Muscle, Smooth, Vascular / Q000166:cytology* / Q000201:enzymology; D010766:Phosphorylation; D019000:Phosphotyrosine; D010982:Platelet-Derived Growth Factor / Q000494:pharmacology*; D012313:RNA / Q000032:analysis; D011817:Rabbits; D015398:Signal Transduction / Q000502:physiology*; D010738:Type C Phospholipases / Q000235:genetics / Q000378:metabolism*; D014443:Tyrosine / Q000031:analogs & derivatives / Q000378:metabolism
D046911:Macromolecular Substances; D010982:Platelet-Derived Growth Factor; D019000:Phosphotyrosine; D014443:Tyrosine; D012313:RNA; D010738:Type C Phospholipases