Differential mechanisms of inositol phosphate generation at the receptors for bombesin and platelet-derived growth factor.
We investigated the mechanism(s) whereby activation of a growth-factor receptor typically endowed with tyrosine kinase activity, such as the platelet-derived growth factor (PDGF) receptor, triggers phosphoinositide hydrolysis. In Swiss 3T3 cells permeabilized with streptolysin O, an analogue of GTP, guanosine 5'-[gamma-thio]triphosphate, was found to potentiate the coupling of the bombesin receptor to phospholipase C. In contrast, the activation of the enzyme by PDGF occurred in a GTP-independent manner. Moreover, the inactive analogue of GTP, guanosine 5'-[beta-thio]diphosphate, significantly inhibited the bombesin-induced InsP3 generation, whereas it did not decrease the same effect when stimulated by PDGF.
Cattaneo
M G
MG
Department of Pharmacology, School of Medicine, University of Milano, Italy.
Vicentini
L M
LM
D000818:Animals; D001839:Bombesin; D002463:Cell Membrane Permeability; D004789:Enzyme Activation; D016244:Guanosine 5'-O-(3-Thiotriphosphate); D006153:Guanosine Diphosphate / Q000494:pharmacology / Q000031:analogs & derivatives; D006160:Guanosine Triphosphate / Q000494:pharmacology; D015544:Inositol 1,4,5-Trisphosphate / Q000378:metabolism; D007295:Inositol Phosphates / Q000378:metabolism*; D051379:Mice; D010982:Platelet-Derived Growth Factor; D018004:Receptors, Bombesin; D011956:Receptors, Cell Surface / Q000502:physiology*; D017981:Receptors, Neurotransmitter / Q000502:physiology*; D017479:Receptors, Platelet-Derived Growth Factor; D013873:Thionucleotides / Q000494:pharmacology; D010738:Type C Phospholipases / Q000378:metabolism
D007295:Inositol Phosphates; D010982:Platelet-Derived Growth Factor; D018004:Receptors, Bombesin; D011956:Receptors, Cell Surface; D017981:Receptors, Neurotransmitter; D013873:Thionucleotides; D006153:Guanosine Diphosphate; C032829:6-thioguanosine 5'-diphosphate; D016244:Guanosine 5'-O-(3-Thiotriphosphate); D015544:Inositol 1,4,5-Trisphosphate; D006160:Guanosine Triphosphate; D017479:Receptors, Platelet-Derived Growth Factor; D010738:Type C Phospholipases; D001839:Bombesin