An EGF receptor-mediated signal attenuates the inhibitory effect of LPA on an adenylate cyclase activity.
A tyrosine kinase receptor-mediated and a heterotrimeric G protein-coupled receptor-mediated signals have been shown to evoke distinct intracellular signaling events. There has been increasing evidence that cross-talk exists between a tyrosine kinase receptor-mediated and a heterotrimeric G protein-coupled receptor-mediated signal transduction pathways. In the present study, we have studied effects of EGF receptor activation on activities of inhibitory G protein (Gi). We show that the amounts of Gi/Go ADP-ribosylated by islet-activating protein (IAP) increased by 30-40% in the membranes of Rat 1 fibroblast cells pretreated with EGF compared with those without pretreatment. When an effect of lysophosphatidic acid (LPA) stimulation on an adenylate cyclase activity was examined, LPA partly attenuated forskolin-stimulated adenylate cyclase activity via Gi because IAP pretreatment blocked the inhibitory effect of LPA. Pretreatment with EGF reduced the ability of LPA to inhibit the forskolin-stimulated adenylate cyclase activity, while the pretreatment did not have any effects on the forskolin-stimulated activity. Thus, the EGF receptor-mediated signal appears to cause the impairment of Gi function in Rat 1 fibroblast cells.
Arimura
S
S
Department of Pharmacology, National Defense Medical College, Tokorozawa, Japan.
Saito
Y
Y
Nakata
H
H
Fukushima
K
K
Nishio
E
E
Watanabe
Y
Y
D037361:Adenylate Cyclase Toxin; D000262:Adenylyl Cyclases / Q000378:metabolism*; D000818:Animals; D002462:Cell Membrane / Q000187:drug effects / Q000378:metabolism; D002478:Cells, Cultured; D005576:Colforsin / Q000494:pharmacology; D004815:Epidermal Growth Factor / Q000494:pharmacology; D066246:ErbB Receptors / Q000378:metabolism*; D005347:Fibroblasts / Q000187:drug effects* / Q000378:metabolism; D019204:GTP-Binding Proteins / Q000378:metabolism; D008246:Lysophospholipids / Q000494:pharmacology*; D037342:Pertussis Toxin; D051381:Rats; D020239:Receptor Cross-Talk / Q000502:physiology*; D015398:Signal Transduction; D010566:Virulence Factors, Bordetella / Q000494:pharmacology
D037361:Adenylate Cyclase Toxin; D008246:Lysophospholipids; D010566:Virulence Factors, Bordetella; D005576:Colforsin; D004815:Epidermal Growth Factor; D037342:Pertussis Toxin; D066246:ErbB Receptors; D019204:GTP-Binding Proteins; D000262:Adenylyl Cyclases