Opposing effects of a ras oncogene on growth factor-stimulated phosphoinositide hydrolysis: desensitization to platelet-derived growth factor and enhanced sensitivity to bradykinin
Expression of a transforming Harvey or Kirsten ras gene caused opposing effects in the ability of platelet-derived growth factor (PDGF) and bradyknin to activate phospholipase C-mediated phosphoinositide hydrolysis. In (/sup 3/H)inositol-labeled rat-1 fibroblasts, PDGF resulted in a 2-fold increase in the level of (/sup 3/H)inositol trisphosphate (InsP/sub 3/) after 2 min and, in the presence of LiCl, a 3- to 8-fold increase in the level of (/sup 3/H)inositol monophosphate (InsP/sub 1/) after 30 min. However, in EJ-ras-transfected rat-1 cells, which exhibit near normal levels of PDGF receptors, PDGF resulted in little or no accumulation of either (/sup 3/H)InsP/sub 3/ or (/sup 3/H)InsP/sub 1/. Similarly, marked stimulations by PDGF were observed in NIH 3T3 cells, as well as in v-src-transformed 3T3 cells, but not in 3T3 cells transformed by Kirsten sarcoma virus or by transfection with v-Ha-ras DNA. This diminished phosphoinositide response in ras-transformed cells was associated with a markedly attenuated mitogenic response to PDGF. On the other hand, both phosphoinositide metabolism and DNA synthesis in ras-transformed fibroblasts were stimulated several-fold by serum. In NIH 3T3 cells carrying a glucocorticoid-inducible v-Ha-ras gene, a close correlation was found between the expression of p21/sup ras/ and the loss of PDGF-stimulated (/sup 3/H)InsP/sub 1/ accumulation. The authors propose that a ras gene product (p21) can, directly or indirectly, influence growth factor-stimulated phosphoinositide hydrolysis, as well as DNA synthesis, via alterations in the properties of specific growth factor receptors.
- Research Organization:
- Cornell Univ., Ithaca, NY (United States)
- OSTI ID:
- 5942622
- Journal Information:
- Proc. Natl. Acad. Sci. U.S.A.; (United States), Vol. 84:9
- Country of Publication:
- United States
- Language:
- English
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BRADYKININ
UPTAKE
LABELLED COMPOUNDS
ONCOGENES
BIOCHEMISTRY
PEPTIDES
ANIMAL GROWTH
BLOOD PLATELETS
CELL CULTURES
FIBROBLASTS
HYDROLYSIS
IODINE 125
LITHIUM CHLORIDES
PHOSPHOLIPIDS
RATS
RECEPTORS
TRITIUM COMPOUNDS
ALKALI METAL COMPOUNDS
ANIMAL CELLS
ANIMALS
BETA DECAY RADIOISOTOPES
BIOLOGICAL MATERIALS
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BODY FLUIDS
CHEMICAL REACTIONS
CHEMISTRY
CHLORIDES
CHLORINE COMPOUNDS
CONNECTIVE TISSUE CELLS
DAYS LIVING RADIOISOTOPES
DECOMPOSITION
ELECTRON CAPTURE RADIOISOTOPES
ESTERS
GENES
GROWTH
HALIDES
HALOGEN COMPOUNDS
INTERMEDIATE MASS NUCLEI
IODINE ISOTOPES
ISOTOPES
KININS
LIPIDS
LITHIUM COMPOUNDS
LITHIUM HALIDES
LYSIS
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ODD-EVEN NUCLEI
ORGANIC COMPOUNDS
ORGANIC PHOSPHORUS COMPOUNDS
POLYPEPTIDES
PROTEINS
RADIOISOTOPES
RODENTS
SOLVOLYSIS
SOMATIC CELLS
VERTEBRATES
550201* - Biochemistry- Tracer Techniques