Control of EGF receptor function by protein kinase C
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
- Resource Relation:
- Other Information: Thesis (Ph. D)
- Country of Publication:
- United States
- Language:
- English
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PEPTIDE HORMONES
RECEPTORS
PHORBOL ESTERS
BIOLOGICAL EFFECTS
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BIOLOGICAL FUNCTIONS
CARCINOMAS
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MAN
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TRACER TECHNIQUES
TUMOR CELLS
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CARCINOGENS
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LIGHT NUCLEI
MAMMALS
MEMBRANE PROTEINS
NEOPLASMS
NUCLEI
ODD-ODD NUCLEI
ORGANIC COMPOUNDS
PHOSPHORUS-GROUP TRANSFERASES
PRIMATES
PROTEINS
RADIOISOTOPES
SODIUM ISOTOPES
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