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 divided by the addition of platelet-derived growth factor (PDGF)-BB. In density-arrested (nonstarved) cells, PDGF-BB affords protection from cell death without stimulation of cell division. In both cultivation conditions the cells express similar amounts of PDGF beta-receptors and the receptor kinase activity was identical as judged by its autophosphorylation capacity. Three signaling pathways were studied in detail: 1) Phospholipase C-gamma (PLC-gamma) and [Ca2+]i increase, 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 regarding PLC-gamma activation, increase of [Ca2+]i, and stimulation of PI-3 kinase activity. But most remarkably the activation of MAP-I was largely suppressed in nonstarved cells. The implications of these signaling pathways in cell protection or cell division are discussed.
Department of Physiological Chemistry, Theodor-Boveri-Institut für Biowissenschaften (Biozentrum), University of Würzburg, Germany.
J
J
Hoppe
V
V
Hoppe
T A
TA
Karenberg
A
A
Fenn
A
A
Simm
A
A
Sachinidis
D000818:Animals; D000077214:Becaplermin; D002118:Calcium / Q000378:metabolism; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000378:metabolism; D002455:Cell Division; D002460:Cell Line; D004789:Enzyme Activation; D005347:Fibroblasts / Q000166:cytology / Q000201:enzymology*; D007294:Inositol / Q000378:metabolism; D007425:Intracellular Membranes / Q000378:metabolism; D051379:Mice; D008934:Mitogens / Q000494:pharmacology*; D010982:Platelet-Derived Growth Factor / Q000494:pharmacology*; D011494:Protein Kinases / Q000378:metabolism*; D020574:Proto-Oncogene Proteins c-sis; D017978:Receptors, Growth Factor / Q000378:metabolism; D011994:Recombinant Proteins; D015398:Signal Transduction
D008934:Mitogens; D010982:Platelet-Derived Growth Factor; D020574:Proto-Oncogene Proteins c-sis; D017978:Receptors, Growth Factor; D011994:Recombinant Proteins; D000077214:Becaplermin; D007294:Inositol; D011494:Protein Kinases; D017871:Calcium-Calmodulin-Dependent Protein Kinases; D002118:Calcium