Pro-Leu-Ser/Thr-Pro is a consensus primary sequence for substrate protein phosphorylation. Characterization of the phosphorylation of c-myc and c-jun proteins by an epidermal growth factor receptor threonine 669 protein kinase
Biochemistry & Molecular Pharmacology
Program in Molecular Medicine; Department of Biochemistry and Molecular Pharmacology
Medical Subject Headings
Amino Acid Sequence; Animals; Chickens; DNA-Binding Proteins; Humans; Mice; Molecular Sequence Data; Peptide Mapping; Phosphorylation; Protein-Tyrosine Kinases; Proto-Oncogene Proteins c-jun; Proto-Oncogene Proteins c-myc; Rats; Receptor, Epidermal Growth Factor; Sequence Alignment; Substrate Specificity; Transcription Factors
Biochemistry, Biophysics, and Structural Biology | Life Sciences | Medicine and Health Sciences
A growth factor-stimulated (MAP2-related) protein kinase, ERT, that phosphorylates the epidermal growth factor receptor at Thr669 has been purified from KB human tumor cells by Northwood and co-workers (Northwood, I. C., Gonzalez, F. A., Wartmann, M., Raden, D. L., and Davis, R. J. (1991) J. Biol. Chem. 266, 15266-15276). The ERT protein kinase has a restricted substrate specificity, and the structural determinants employed for substrate recognition by this enzyme have not been defined. As an approach toward understanding the specificity of substrate phosphorylation, we have used an in vitro assay to identify additional substrates for the ERT protein kinase. In this report we describe two novel substrates: (a) the human c-myc protein at Ser62 and (b) the rat c-jun protein at Ser246. Alignment of the primary sequences surrounding the phosphorylation sites located within the epidermal growth factor receptor (Thr669), Myc (Ser62), and Jun (Ser246) demonstrated a marked similarity. The observed consensus sequence was Pro-Leu-Ser/Thr-Pro. We propose that this sequence forms part of a substrate structure that is recognized by the ERT protein kinase.
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Citation: J Biol Chem. 1991 Aug 15;266(23):15277-85.
The Journal of biological chemistry
Alvarez, Elvira; Northwood, Ingrid C.; Gonzalez, Fernando A.; Latour, Debra A.; Seth, Alpna; Abate, Cory; Curran, Tom; and Davis, Roger J., "Pro-Leu-Ser/Thr-Pro is a consensus primary sequence for substrate protein phosphorylation. Characterization of the phosphorylation of c-myc and c-jun proteins by an epidermal growth factor receptor threonine 669 protein kinase" (1991). GSBS Student Publications. 45.