Mechanisms of specificity in protein phosphorylation.
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.
Ubersax
Jeffrey A
JA
Department of Chemical and Systems Biology, Stanford University School of Medicine, Stanford, California 94305-5174, USA. jubersax@stanford.edu
Ferrell
James E
JE
D000244:Adenosine Diphosphate / Q000378:metabolism; D000255:Adenosine Triphosphate / Q000378:metabolism; D020816:Amino Acid Motifs; D000595:Amino Acid Sequence; D000818:Animals; D001665:Binding Sites; D016384:Consensus Sequence; D005544:Forecasting; D006801:Humans; D057927:Hydrophobic and Hydrophilic Interactions; D051379:Mice; D008954:Models, Biological; D008958:Models, Molecular; D041681:NIH 3T3 Cells; D010766:Phosphorylation; D011485:Protein Binding; D011494:Protein Kinases / Q000737:chemistry / Q000145:classification / Q000378:metabolism*; D017433:Protein Structure, Secondary; D017434:Protein Structure, Tertiary; D055672:Static Electricity; D013379:Substrate Specificity
D000244:Adenosine Diphosphate; D000255:Adenosine Triphosphate; D011494:Protein Kinases