Abstract
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.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Bombesin*
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Cell Membrane Permeability
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Enzyme Activation
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Guanosine 5'-O-(3-Thiotriphosphate)
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Guanosine Diphosphate / pharmacology
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Guanosine Triphosphate / pharmacology
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Inositol 1,4,5-Trisphosphate / metabolism
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Inositol Phosphates / metabolism*
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Mice
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Platelet-Derived Growth Factor*
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Receptors, Bombesin
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Receptors, Cell Surface / physiology*
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Receptors, Neurotransmitter / physiology*
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Receptors, Platelet-Derived Growth Factor
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Thionucleotides / pharmacology
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Type C Phospholipases / metabolism
Substances
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Inositol Phosphates
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Platelet-Derived Growth Factor
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Receptors, Bombesin
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Receptors, Cell Surface
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Receptors, Neurotransmitter
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Thionucleotides
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Guanosine Diphosphate
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6-thioguanosine 5'-diphosphate
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Guanosine 5'-O-(3-Thiotriphosphate)
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Inositol 1,4,5-Trisphosphate
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Guanosine Triphosphate
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Receptors, Platelet-Derived Growth Factor
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Type C Phospholipases
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Bombesin