Role of tyrosine kinase and membrane-spanning domains in signal transduction by the platelet-derived growth factor receptor.
Three types of mutations were introduced into the platelet-derived growth factor (PDGF) receptor to cause a loss of PDGF-stimulated tyrosine kinase activity: (i) a point mutation of the ATP-binding site, (ii) a deletion of the carboxyl-terminal region, and (iii) replacement of the membrane-spanning sequences by analogous transmembrane sequences of other receptors. Transfectants expressing mutated receptors bind, 125I-labeled PDGF with a high affinity but had no PDGF-sensitive tyrosine kinase activity, phosphatidylinositol turnover, increase in the intracellular calcium concentration, change in cellular pH, or stimulation of DNA synthesis. However, PDGF-induced receptor down regulation was normal in the mutant cells. These results indicate that the transmembrane sequence has a specific signal-transducing function other than merely serving as a membrane anchor and that the receptor kinase activity is necessary for most responses to PDGF but is not required for receptor down regulation.
Escobedo
J A
JA
Howard Hughes Medical Institute, University of California, San Francisco 94143-0724.
Barr
P J
PJ
Williams
L T
LT
D000818:Animals; D002460:Cell Line; D002462:Cell Membrane / Q000502:physiology; D002872:Chromosome Deletion; D004261:DNA Replication; D005796:Genes; D007295:Inositol Phosphates / Q000378:metabolism; D009154:Mutation; D010716:Phosphatidylinositols / Q000378:metabolism; D010982:Platelet-Derived Growth Factor / Q000502:physiology*; D011505:Protein-Tyrosine Kinases / Q000378:metabolism*; D011956:Receptors, Cell Surface / Q000235:genetics / Q000502:physiology*; D017479:Receptors, Platelet-Derived Growth Factor; D015398:Signal Transduction; D014162:Transfection
D007295:Inositol Phosphates; D010716:Phosphatidylinositols; D010982:Platelet-Derived Growth Factor; D011956:Receptors, Cell Surface; D011505:Protein-Tyrosine Kinases; D017479:Receptors, Platelet-Derived Growth Factor