Phosphoinositide hydrolysis in Ki-ras-transformed fibroblasts stimulated by platelet-derived growth factor and bradykinin.
Signal transduction in response to platelet-derived growth factor (PDGF)-BB and bradykinin (BK) have been examined by measuring inositol polyphosphate formation in NIH3T3 fibroblast and v-Ki-ras-transformed NIH3T3 fibroblast (DT). The PDGF-induced inositol polyphosphate formation in NIH3T3 was greater than that in DT cells, in which autophosphorylation of PDGF receptor and tyrosine phosphorylation of phospholipase C (PLC)-gamma 1 were suppressed when examined by immunoblotting with anti-phosphotyrosine antibody. On the other hand, BK-stimulation produced a much higher level of inositol polyphosphate in DT cells which have a greater number of BK receptors. These results indicate that in Ki-ras transformed cells the decrease (caused by PDGF) and the increase (caused by BK) in phosphoinositide hydrolysis are due to the defective autophosphorylation of PDGF receptors leading to a reduction in PLC-gamma 1 tyrosine phosphorylation and the overexpression of BK receptors, respectively.
Kumada
T
T
Department of Otolaryngology, Gifu University School of Medicine, Japan.
Banno
Y
Y
Miyata
H
H
Nozawa
Y
Y
D016475:3T3 Cells; D000818:Animals; D000077214:Becaplermin; D001920:Bradykinin / Q000494:pharmacology*; D002461:Cell Line, Transformed; D002471:Cell Transformation, Neoplastic; D004591:Electrophoresis, Polyacrylamide Gel; D011905:Genes, ras; D006868:Hydrolysis; D015151:Immunoblotting; D051379:Mice; D008970:Molecular Weight; D010716:Phosphatidylinositols / Q000378:metabolism*; D010766:Phosphorylation; D010982:Platelet-Derived Growth Factor / Q000494:pharmacology*; D020574:Proto-Oncogene Proteins c-sis; D018002:Receptors, Bradykinin / Q000378:metabolism; D011994:Recombinant Proteins / Q000494:pharmacology; D015398:Signal Transduction / Q000187:drug effects*; D014162:Transfection
D010716:Phosphatidylinositols; D010982:Platelet-Derived Growth Factor; D020574:Proto-Oncogene Proteins c-sis; D018002:Receptors, Bradykinin; D011994:Recombinant Proteins; D000077214:Becaplermin; D001920:Bradykinin