Opposing effects of a ras oncogene on growth factor-stimulated phosphoinositide hydrolysis: desensitization to platelet-derived growth factor and enhanced sensitivity to bradykinin

Journal Article · Fri May 01 04:00:00 EDT 1987 · Proc. Natl. Acad. Sci. U.S.A.; (United States)

DOI:https://doi.org/10.1073/pnas.84.9.2648· OSTI ID:5942622

Parries, G; Hoebel, R; Racker, E

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
• OSTI ID: 5942622
• Journal Information: Proc. Natl. Acad. Sci. U.S.A.; (United States), Journal Name: Proc. Natl. Acad. Sci. U.S.A.; (United States) Vol. 84:9; ISSN PNASA
• Country of Publication: United States
• Language: English

Related Subjects

550201* -- Biochemistry-- Tracer Techniques
59 BASIC BIOLOGICAL SCIENCES
ALKALI METAL COMPOUNDS
ANIMAL CELLS
ANIMAL GROWTH
ANIMALS
BETA DECAY RADIOISOTOPES
BIOCHEMISTRY
BIOLOGICAL MATERIALS
BLOOD
BLOOD CELLS
BLOOD PLATELETS
BODY FLUIDS
BRADYKININ
CELL CULTURES
CHEMICAL REACTIONS
CHEMISTRY
CHLORIDES
CHLORINE COMPOUNDS
CONNECTIVE TISSUE CELLS
DAYS LIVING RADIOISOTOPES
DECOMPOSITION
ELECTRON CAPTURE RADIOISOTOPES
ESTERS
FIBROBLASTS
GENES
GROWTH
HALIDES
HALOGEN COMPOUNDS
HYDROLYSIS
INTERMEDIATE MASS NUCLEI
IODINE 125
IODINE ISOTOPES
ISOTOPES
KININS
LABELLED COMPOUNDS
LIPIDS
LITHIUM CHLORIDES
LITHIUM COMPOUNDS
LITHIUM HALIDES
LYSIS
MAMMALS
MATERIALS
MEMBRANE PROTEINS
NUCLEI
ODD-EVEN NUCLEI
ONCOGENES
ORGANIC COMPOUNDS
ORGANIC PHOSPHORUS COMPOUNDS
PEPTIDES
PHOSPHOLIPIDS
POLYPEPTIDES
PROTEINS
RADIOISOTOPES
RATS
RECEPTORS
RODENTS
SOLVOLYSIS
SOMATIC CELLS
TRITIUM COMPOUNDS
UPTAKE
VERTEBRATES