Loss of platelet-derived growth factor-stimulated phospholipase activity in NIH-3T3 cells expressing the EJ-ras oncogene

Journal Article · Thu Jan 01 04:00:00 EST 1987 · Proc. Natl. Acad. Sci. U.S.A.; (United States)

DOI:https://doi.org/10.1073/pnas.84.2.546· OSTI ID:6215369

Benjamin, C W; Tarpley, W G; Gorman, R R

Data indicating that the 21-kDa protein (p21) Harvey-ras gene product shares sequence homology with guanine nucleotide-binding proteins (G proteins) has stimulated research on the influence(s) of p21 on G-protein-regulated systems in vertebrate cells. Previous work demonstrated that NIH-3T3 mouse cells expressing high levels of the cellular ras oncogene isolated from the EJ human bladder carcinoma (EJ-ras) exhibited reduced hormone-stimulated adenylate cyclase activity. The authors now report that in these cells another enzyme system thought to be regulated by G proteins is inhibited, namely phospholipases A/sub 2/ and C. NIH-3T3 cells incubated in plasma-derived serum release significant levels of prostaglandin E/sub 2/ (PGE/sub 2/) as determined by radioimmunoassay when exposed to platelet-derived growth factor (PDGF) at 2 units/ml. The lack of PDGF-stimulated PGE/sub 2/ release from EJ-ras-transfected cells is not due to a defect in the prostaglandin cyclooxygenase enzyme, since incubation of control cells and EJ-ras-transfected cells in 0.33, 3.3, or 33 ..mu..M arachidonate resulted in identical levels of PGE/sub 2/ release. The lack of PDGF-stimulated PGE/sub 2/ release from EJ-ras-transfected cells also does not result from the loss of functional PDGF receptors. EJ-ras-transformed cells bind 70% as much /sup 125/I-labeled PDGF as control cells and are stimulated to incorporate (/sup 3/H)thymidine and to proliferate after exposure to PDGF. Determination of total water-soluble inositolphospholipids and changes in the specific activities of phosphatidylcholine in control and EJ-ras-transfected cells demonstrated that PDGF-stimulated phospholipase C and A/sub 2/ activities are inhibited in the EJ-ras-transfected cells.

• Research Organization: Upjohn Co., Kalamazoo, MI
• OSTI ID: 6215369
• Journal Information: Proc. Natl. Acad. Sci. U.S.A.; (United States), Journal Name: Proc. Natl. Acad. Sci. U.S.A.; (United States) Vol. 84:2; ISSN PNASA
• Country of Publication: United States
• Language: English

Related Subjects

550601* -- Medicine-- Unsealed Radionuclides in Diagnostics
550602 -- Medicine-- External Radiation in Diagnostics-- (1980-)
62 RADIOLOGY AND NUCLEAR MEDICINE
ANIMAL CELLS
ARACHIDONIC ACID
AZINES
BIOLOGICAL MATERIALS
BLOOD
BLOOD CELLS
BLOOD PLATELETS
BODY FLUIDS
CARBOXYLESTERASES
CARBOXYLIC ACIDS
CELL TRANSFORMATIONS
CHROMATOGRAPHY
CONFIGURATION INTERACTION
CONNECTIVE TISSUE CELLS
ENZYME ACTIVITY
ENZYMES
ESTERASES
ESTERS
FIBROBLASTS
GENES
GROWTH
HETEROCYCLIC COMPOUNDS
HYDROLASES
IMMUNOASSAY
IMMUNOLOGY
ISOTOPE APPLICATIONS
LABELLED COMPOUNDS
LIPASE
LIPIDS
MATERIALS
MONOCARBOXYLIC ACIDS
NUCLEOSIDES
NUCLEOTIDES
ONCOGENES
ONCOGENIC TRANSFORMATIONS
ORGANIC ACIDS
ORGANIC COMPOUNDS
ORGANIC NITROGEN COMPOUNDS
ORGANIC PHOSPHORUS COMPOUNDS
PHOSPHOLIPIDS
PROSTAGLANDINS
PROTEINS
PYRIMIDINES
RADIOASSAY
RADIOIMMUNOASSAY
RADIOIMMUNOLOGY
RIBOSIDES
SEPARATION PROCESSES
SOMATIC CELLS
THIN-LAYER CHROMATOGRAPHY
THYMIDINE
TIME DEPENDENCE
TRACER TECHNIQUES
TRITIUM COMPOUNDS