DIFFERENTIAL ACTIVATION BY PLATELET-DERIVED GROWTH FACTOR-BB OF MITOGEN-ACTIVATED PROTEIN-KINASES IN STARVED OR NONSTARVED AKR-2B FIBROBLASTS

More than 90% of serum-deprived (starved) AKR-2B mouse fibroblasts are stimulated to divide by the addition of platelet-derived growth facto r (PDCF)-BB. In density-arrested (nonstarved) cells, PDGF-BB affords p rotection from cell death without stimulation of cell division. In bot h cultivation conditions the cells express similar amounts of PDGF bet a-receptors and the receptor kinase activity was identical as judged b y its autophosphorylation capacity. Three signaling pathways were stud ied in detail: 1) Phospholipase C-gamma (PLC-gamma) and [Ca2+](i) incr ease, 2) activation of the phosphatidylinositol-3 kinase (PI-3 kinase) , and 3) activation of mitogen activated kinases I and II (MAP kinases I and II). There was no difference in starved or nonstarved cells reg arding PLC-gamma activation, increase of [Ca2+](i), and stimulation oi PI-3 kinase activity. But most remarkably the activation of MAP-I was largely suppressed in nonstarved cells. The implications of these sig naling pathways in cell protection or cell division are discussed. (C) 1994 Wiley-Liss, Inc.