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Trends Biochem Sci. 2018 May;43(5):380-394. doi: 10.1016/j.tibs.2018.02.009. Epub 2018 Mar 12.

Homing in: Mechanisms of Substrate Targeting by Protein Kinases.

Author information

1
Department of Pharmacology, Yale School of Medicine, New Haven, CT 06520, USA.
2
Department of Pharmacology, Yale School of Medicine, New Haven, CT 06520, USA. Electronic address: ben.turk@yale.edu.

Abstract

Protein phosphorylation is the most common reversible post-translational modification in eukaryotes. Humans have over 500 protein kinases, of which more than a dozen are established targets for anticancer drugs. All kinases share a structurally similar catalytic domain, yet each one is uniquely positioned within signaling networks controlling essentially all aspects of cell behavior. Kinases are distinguished from one another based on their modes of regulation and their substrate repertoires. Coupling specific inputs to the proper signaling outputs requires that kinases phosphorylate a limited number of sites to the exclusion of hundreds of thousands of off-target phosphorylation sites. Here, we review recent progress in understanding mechanisms of kinase substrate specificity and how they function to shape cellular signaling networks.

KEYWORDS:

enzyme specificity; linear sequence motif; protein interactions; protein kinase; protein phosphorylation

PMID:
29544874
PMCID:
PMC5923429
DOI:
10.1016/j.tibs.2018.02.009
[Indexed for MEDLINE]
Free PMC Article

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