Mechanisms of specificity in protein phosphorylation

• Published in: Nature reviews. Molecular cell biology Vol. 8; no. 7; pp. 530 - 541
• Main Authors: Ubersax, Jeffrey A, Ferrell Jr, James E
• Format: Journal Article
• Language: English
• Published: England Nature Publishing Group 01.07.2007
• Subjects: Adenosine Diphosphate - metabolism; Adenosine Triphosphate - metabolism; Amino Acid Motifs; Amino Acid Sequence; Amino acids; Animals; Binding Sites; Consensus Sequence; Cyclin-dependent kinases; Forecasting; Humans; Hydrophobic and Hydrophilic Interactions; Insulin; Kinases; Methods; Mice; Models, Biological; Models, Molecular; NIH 3T3 Cells; Phosphorylation; Physiological aspects; Post-translational modification; Protein Binding; Protein kinases; Protein Kinases - chemistry; Protein Kinases - classification; Protein Kinases - metabolism; Protein Structure, Secondary; Protein Structure, Tertiary; Proteins; Signal transduction; Static Electricity; Substrate Specificity; Substrates; United States
• ISSN: 1471-0072; 1471-0080
• DOI: 10.1038/nrm2203

A typical protein kinase must recognize between one and a few hundred bona fide phosphorylation sites in a background of approximately 700,000 potentially phosphorylatable residues. Multiple mechanisms have evolved that contribute to this exquisite specificity, including the structure of the catalytic site, local and distal interactions between the kinase and substrate, the formation of complexes with scaffolding and adaptor proteins that spatially regulate the kinase, systems-level competition between substrates, and error-correction mechanisms. The responsibility for the recognition of substrates by protein kinases appears to be distributed among a large number of independent, imperfect specificity mechanisms.