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Epidermal growth factor stimulates phosphorylation of RAF-1 independently of receptor autophosphorylation and internalization

: Gill, G.N.; Stanley, E.R.; Baccarini, M.

The Journal of biological chemistry 266 (1991), Nr.17, S.10941-10945
ISSN: 0021-9258
ISSN: 1083-351X
Fraunhofer ITA ( ITEM) ()
EGF; epidermal growth factor; epidermal growth factor receptor; protein-tyrosine kinase; proto-oncogene protein; urogastrone

Phosphorylation of the RAF-1 protooncogene product and activation of its associated serine/threonine kinase are common features of the response of cells to peptide growth factors. We have used wild-type and mutant epidermal growth factor (EGF) receptors to investigate mechanisms of RAF-1 phosphorylation. In vivo EGF treatment rapidly stimulated phosphorylation of RAF-1 exclusively on serine residues. Stimulation of RAF-1 phosphorylation occurred at 37 degrees C but not at 4 degrees C and persisted after dissociation of EGF from its receptor. EGF-induced RAF-1 serine phosphorylation required the intrinsic tyrosine kinase activity of the EGF receptor but was independent of EGF receptor self-phosphorylation and of ligand-induced receptor internalization. Down-regulation of protein kinase C did not affect the EGF-induced increase in RAF-1 phosphorylation. These data suggest that the activated tyrosine kinase activity of the EGF receptor enhances serine phosphorylation of RAF-1 via an inter mediary molecule(s).