Influence of a ras oncogene on platelet-derived growth factor (PDGF)-stimulated phosphoinositide hydrolysis in murine fibroblasts
The authors have examined the effects of transfection of rat-1 fibroblasts with the ras oncogene on the metabolism of phosphatidylinositol (PI). Incubation of (/sup 3/H)inositol-labeled rat-1 cells with PDGF resulted in a 2- to 3-fold increase in (/sup 3/H)IP3 levels within 90 s. In the presence of 25 mM Li+, (/sup 3/H)IP1 levels were increased 8-fold after 30 min. In contrast, incubation of ras-transfected fibroblasts (EJ-2 line) with PDGF had little or no effect on the level of either (/sup 3/H)IP3 or (/sup 3/H)IP1. Similar stimulations by PDGF were observed in NIH 3T3 cells, but not in Kirsten virus-transformed or Harvey ras-transfected cell lines. On the other hand, NIH 3T3 cells transfected with v-src responded to PDGF by stimulation of PI turnover similar to the parent cell line. In NIH 3T3 cells transfected with an expression vector containing the v-Ha-ras gene under transcriptional control of the glucocorticoid-inducible mouse mammary tumor virus promoter, the PDGF stimulation of (/sup 3/H)inositol incorporation into PI was reduced from 10-fold in the absence of dexamethasone to 1.8-fold when the cells were pretreated for 26 h with 2 ..mu..M dexamethasone. In the parental 3T3 cells PDGF stimulation was reduced by about 40% in the presence of dexamethasone. In the absence of PDGF the rate of PI turnover (i.e., the kinetics of (/sup 3/H)IP1 accumulation in the presence of Li+) in EJ-2 cells was similar to that in rat-1 cells. Thus, in the presence of PDGF, the rate of PI turnover in rat-1 cells was several fold higher than in the transfected cells. These results suggest that the ras gene product (p21) may exert an inhibitory effect on PDGF-stimulated phosphoinositide metabolism.
- Research Organization:
- Cornell Univ., Ithaca, NY
- OSTI ID:
- 7035463
- Report Number(s):
- CONF-8606151-; TRN: 87-010314
- Journal Information:
- Fed. Proc., Fed. Am. Soc. Exp. Biol.; (United States), Vol. 45:6; Conference: 76. annual meeting of the Federation of American Society for Experimental Biology, Washington, DC, USA, 8 Jun 1986
- Country of Publication:
- United States
- Language:
- English
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Related Subjects
ONCOGENES
BIOCHEMICAL REACTION KINETICS
PHOSPHOLIPIDS
METABOLISM
PROTEINS
BIOLOGICAL EFFECTS
DEXAMETHASONE
FIBROBLASTS
RATS
TRACER TECHNIQUES
TRITIUM COMPOUNDS
ADRENAL HORMONES
ANIMAL CELLS
ANIMALS
CONNECTIVE TISSUE CELLS
CORTICOSTEROIDS
ESTERS
GENES
GLUCOCORTICOIDS
HORMONES
HYDROXY COMPOUNDS
ISOTOPE APPLICATIONS
KETONES
KINETICS
LABELLED COMPOUNDS
LIPIDS
MAMMALS
ORGANIC COMPOUNDS
ORGANIC PHOSPHORUS COMPOUNDS
PREGNANES
REACTION KINETICS
RODENTS
SOMATIC CELLS
STEROID HORMONES
STEROIDS
VERTEBRATES
550201* - Biochemistry- Tracer Techniques