Epidermal growth factor stimulates phosphorylation of eukaryotic initiation factor 4B, independently of protein kinase C.
We demonstrate that exposure of human epidermoid carcinoma A431 cells to epidermal growth factor (EGF) results in phosphorylation of eIF-4B within minutes after addition of EGF. The EGF-induced phosphorylation of eIF-4B is not caused by the EGF receptor tyrosine kinase itself, since no tyrosine-phosphorylated eIF-4B could be detected upon immunoprecipitation using an anti-phosphotyrosine antibody. Enhanced phosphorylation of eIF-4B was also detected upon exposure of the cells to phorbol 12-myristate 13-acetate (PMA), an activator of protein kinase C (PKC), suggesting that eIF-4B may be a substrate of PKC. However, down-regulation of PKC did not influence the EGF-induced eIF-4B phosphorylation, which indicates that eIF-4B is phosphorylated by an as yet unknown kinase, activated early in the EGF-induced signal transduction cascade.
Department of Molecular Cell Biology, University of Utrecht, The Netherlands.
R M
RM
Wolthuis
A F
AF
Cremers
M A
MA
Kasperaitis
C
C
van der Mast
H O
HO
Voorma
J
J
Boonstra
D004789:Enzyme Activation; D004815:Epidermal Growth Factor / Q000494:pharmacology*; D066246:ErbB Receptors / Q000187:drug effects* / Q000378:metabolism; D039642:Eukaryotic Initiation Factors; D006801:Humans; D010448:Peptide Initiation Factors / Q000378:metabolism*; D010766:Phosphorylation / Q000187:drug effects; D011233:Precipitin Tests; D011493:Protein Kinase C / Q000378:metabolism*; D011505:Protein-Tyrosine Kinases / Q000378:metabolism; D015398:Signal Transduction; D013755:Tetradecanoylphorbol Acetate; D013997:Time Factors; D014407:Tumor Cells, Cultured
D039642:Eukaryotic Initiation Factors; D010448:Peptide Initiation Factors; C031799:eIF-4B; D004815:Epidermal Growth Factor; D066246:ErbB Receptors; D011505:Protein-Tyrosine Kinases; D011493:Protein Kinase C; D013755:Tetradecanoylphorbol Acetate