Mitogen-activated protein kinase stimulation by a tyrosine kinase-negative epidermal growth factor receptor
Department of Biochemistry and Molecular Biology; Program in Molecular Medicine
Amino Acid Sequence; Animals; CHO Cells; Calcium-Calmodulin-Dependent Protein Kinases; Cricetinae; Enzyme Activation; Epidermal Growth Factor; Gene Expression; Humans; Mitogens; Molecular Sequence Data; Mutagenesis; Phosphorylation; Phosphotyrosine; Protein Kinases; Protein-Tyrosine Kinases; Receptor, Epidermal Growth Factor; Signal Transduction; Tyrosine
Life Sciences | Medicine and Health Sciences
Mutation of the epidermal growth factor receptor (EGF-R) within the ATP binding subdomain results in a receptor that lacks tyrosine kinase activity and is defective in signal transduction. However, this kinase-negative EGF-R is able to activate MAP kinase (Campos-Gonzalez, R., and Glenny, J. R. (1992) J. Biol. Chem. 267, 14535-14538). This observation suggests that signal initiation by the EGF-R can occur by a mechanism that is independent of the receptor tyrosine kinase activity. Here, we report that the kinase-negative EGF-R is phosphorylated on tyrosine in EGF-treated cells. The mechanism of tyrosine phosphorylation can be accounted for by the action of EGF to stimulate a protein kinase activity that is associated with the kinase-negative EGF-R. This protein kinase activity is not intrinsic to the receptor and can be separated from the EGF-R by incubation with 0.5 M NaCl. MAP kinase activation by the kinase-negative EGF-R may therefore occur by a mechanism that requires a receptor-associated tyrosine kinase. Thus, it is unnecessary to propose a novel kinase-independent mechanism of signal initiation to account for MAP kinase activation by the kinase-negative EGF-R.
J Biol Chem. 1993 Jan 25;268(3):2250-4.
The Journal of biological chemistry
Selva EM, Raden DL, Davis RJ. (1993). Mitogen-activated protein kinase stimulation by a tyrosine kinase-negative epidermal growth factor receptor. Open Access Articles. Retrieved from https://escholarship.umassmed.edu/oapubs/837