Epidermal growth factor (EGF) promotes phosphorylation at threonine-654 of the EGF receptor: possible role of protein kinase C in homologous regulation of the EGF receptor
Treatment of cells with tumor-promoting phorbol diesters, which causes activation of protein kinase C, leads to phosphorylation of the epidermal growth factor (EGF) receptor at threonine-654. Addition of phorbol diesters to intact cells causes inhibition of the EGF-induced tyrosine-protein kinase activity of the EGF receptor and it has been suggested that this effect of phorbol diesters is mediated by the phosphorylation of the receptor by protein kinase C. The authors measured the activity of protein kinase C in A431 cells by determining the incorporation of (/sup 32/P)phosphate into peptides containing threonine-654 obtained by trypsin digestion of EGF receptors. After 3 h of exposure to serum-free medium, A431 cells had no detectable protein kinase C activity. Addition of EGF to these cells resulted in (/sup 32/P) incorporation into threonine-654 as well as into tyrosine residues. This indicates that EGF promotes the activation of protein kinase C in A431 cells. The phophorylation of threonine-654 induced by EGF was maximal after only 5 min of EGF addition and the (/sup 32/P) incorporation into threonine-654 reached 50% of the (/sup 32/P) in a tyrosine-containing peptide. This indicates that a significant percentage of the total EGF receptors are phosphorylated by protein kinase C. A variety of external stimuli activate Na/sup +//H/sup +/ exchange, including EGF, phorbol diesters, and hypertonicity. To ascertain whether activation of protein kinase C is an intracellular common effector of all of these systems, the authors measured the activity of protein kinase C after exposure of A431 cells to hyperosmotic conditions and observed no effect on phosphorylation of threonine-654, therefore, activation of Na/sup +//H/sup +/ exchange by hypertonic medium is independent of protein kinase C activity.
- Research Organization:
- Washington Univ., St. Louis, MO (United States). School of Medicine
- OSTI ID:
- 6401363
- Journal Information:
- J. Cell Biol.; (United States), Vol. 103:4, Issue 4
- Country of Publication:
- United States
- Language:
- English
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PHORBOL ESTERS
BIOLOGICAL EFFECTS
PHOSPHORUS 32
TRACER TECHNIQUES
RECEPTORS
PHOSPHORYLATION
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GROWTH
PHOSPHOTRANSFERASES
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BETA DECAY RADIOISOTOPES
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NUCLEI
ODD-ODD NUCLEI
ORGANIC COMPOUNDS
ORGANS
PHOSPHORUS ISOTOPES
PHOSPHORUS-GROUP TRANSFERASES
PROTEINS
RADIOISOTOPES
SKIN
TISSUES
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