Kinase Consensus Sequences: A Breeding Ground for Crosstalk

The best characterized,examples of crosstalk between two or more different post-translational modifications (PTMs) occur with respect to histones. These examples demonstrate the critical roles that crosstalk plays in regulating cell signaling pathways. Recently, however, non-histone crosstalk has been observed between serine/threonine phosphorylation and the Modification of arginine and lysine residues within kinase consensus sequences. Interestingly, many kinase consensus sequences contain critical arginine/lysine residues surrounding the substrate serine/threonine residue. Therefore, we hypothesize that non-histone crosstalk between serine/threonine phosphorylation and arginine/lysine, modifications is a global mechanism for the modulation of cellular signaling In this review, we discuss several recent examples of non-histone kinase consensus sequence crosstalk, as well as provide the biophysical basis, for these observations. In addition we predict likely examples of crosstalk between protein arginine methyltransferase 1 (PRMT1) and Akt and discuss the future implications of these findings.