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Control of EGF receptor function by protein kinase C

Thesis/Dissertation ·
OSTI ID:6401115
Treatment of human epidermoid carcinoma A431 cells with nanomolar concentrations of the potent tumor promotor, phorbol 12-myristate 13-acetate (PMA), is shown to attentuate the ability of epidermal growth factor (EGF) or serum to activate Na/sup +//H/sup +/ exchange, which is measured as an amiloride-inhibitable pH/sub i/ increase or /sup 22/Na/sup +/ uptake. The ability of PMA to directly activate Na/sup +//H/sup +/ exchange is also reported, but PMA-induced pH/sub i/ increases are modest with respect to those of EGF or serum and require relatively high concentrations of PMA. The effects of PMA on mitogen receptor-stimulated Na/sup +//H/sup +/ exchange were examined in the mouse fibroblast NR6 cell line using platelet-derived growth factor (PDGF). The results were similar to those in A431 cells, except that PMA in NR6 cells causes pH/sub i/ increases at lower concentrations. Phorbol diester action is mediated by the activity of the enzyme protein kinase C. The results summarized above support the hypothesis that PMA-induced protein kinase C activity opposes mitogenic stimulation. The presumed endogenous PMA analog is diacylglycerol, which is generated by phosphoinositide hydrolysis and has been reported to be produced in response to the mitogens, EGF and PDGF.
Research Organization:
Washington Univ., Seattle (USA)
OSTI ID:
6401115
Country of Publication:
United States
Language:
English

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Related Subjects

550201 -- Biochemistry-- Tracer Techniques
560300* -- Chemicals Metabolism & Toxicology
59 BASIC BIOLOGICAL SCIENCES
63 RADIATION, THERMAL, AND OTHER ENVIRON. POLLUTANT EFFECTS ON LIVING ORGS. AND BIOL. MAT.
ALKALI METAL ISOTOPES
ANIMAL CELLS
ANIMALS
BETA DECAY RADIOISOTOPES
BETA-PLUS DECAY RADIOISOTOPES
BIOLOGICAL EFFECTS
BIOLOGICAL FUNCTIONS
CARCINOGENS
CARCINOMAS
DISEASES
ENZYME ACTIVITY
ENZYMES
ESTERS
FUNCTIONS
HORMONES
ION EXCHANGE
ISOTOPE APPLICATIONS
ISOTOPES
LIGHT NUCLEI
MAMMALS
MAN
MEMBRANE PROTEINS
NEOPLASMS
NUCLEI
ODD-ODD NUCLEI
ORGANIC COMPOUNDS
PEPTIDE HORMONES
PHORBOL ESTERS
PHOSPHORUS-GROUP TRANSFERASES
PHOSPHOTRANSFERASES
PRIMATES
PROTEINS
RADIOISOTOPES
RECEPTORS
SODIUM 22
SODIUM ISOTOPES
TRACER TECHNIQUES
TRANSFERASES
TUMOR CELLS
VERTEBRATES
YEARS LIVING RADIOISOTOPES