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 be...

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Bibliographic Details
Published in:ACS chemical biology 2011-09, Vol.6 (9), p.881-892
Main Authors: Rust, Heather L, Thompson, Paul R
Format: Article
Language:English
Subjects:
Amino Acids - metabolism
Consensus Sequence
Humans
Phosphorylation
Protein Kinases - metabolism
Signal Transduction
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Summary: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.
ISSN:1554-8929
1554-8937
DOI:10.1021/cb200171d