Identification of substrate recognition determinants for human ERK1 and ERK2 protein kinases

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Department of Biochemistry and Molecular Biology; Program in Molecular Medicine

Publication Date


Document Type



Amino Acid Sequence; Cell Line; Humans; Kinetics; Mitogen-Activated Protein Kinase 1; Mitogen-Activated Protein Kinase 3; *Mitogen-Activated Protein Kinases; Molecular Sequence Data; Peptides; Phosphorylation; Protein Kinases; Receptor, Epidermal Growth Factor; Substrate Specificity


Life Sciences | Medicine and Health Sciences


Two epidermal growth factor-stimulated protein kinases that correspond to ERK1 and ERK2 have been purified from human epidermoid carcinoma cells (Northwood, I. C., Gonzalez, F. A., Wartmann, M., Raden, D. L., and Davis, R. J. (1991) J. Biol. Chem. 266, 15266-15276). A consensus primary sequence for substrates of ERK1 has been identified as -Pro-Leu-Ser/Thr-Pro- (Alvarez, E., Northwood, I. C., Gonzalez, F. A., Latour, D. A., Seth, A., Abate, C., Curran, T., and Davis, R. J. (1991) J. Biol. Chem. 266, 15277-15285). However, the structural determinants for substrate recognition are not understood. We performed a systematic analysis of the effect of point mutations in the primary sequence of peptide substrates on the rate of phosphorylation by ERK1 and ERK2. The results of this investigation demonstrate that the substrate specificities of the ERK1 and ERK2 protein kinases are very similar. We propose that the primary sequence of substrates for ERK1 and ERK2 protein kinases can be generalized as -Pro-Xaan-Ser/Thr-Pro- (where Xaa is a neutral or basic amino acid and n = 1 or 2).


J Biol Chem. 1991 Nov 25;266(33):22159-63.

Journal/Book/Conference Title

The Journal of biological chemistry

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