Mechanisms of specificity in protein phosphorylation
Top Cited Papers
- 1 July 2007
- journal article
- review article
- Published by Springer Nature in Nature Reviews Molecular Cell Biology
- Vol. 8 (7) , 530-541
- https://doi.org/10.1038/nrm2203
Abstract
A typical protein kinase must recognize between one and a few hundred bona fide phosphorylation sites in a background of similar to 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.Keywords
This publication has 149 references indexed in Scilit:
- Emerging roles of nuclear protein phosphatasesNature Reviews Molecular Cell Biology, 2007
- Structural basis for the selective inhibition of JNK1 by the scaffolding protein JIP1 and SP600125The EMBO Journal, 2004
- Interaction of the S-phase cyclin Clb5 with an 'RXL' docking sequence in the initiator protein Orc6 provides an origin-localized replication control switchGenes & Development, 2004
- The biological functions of A-kinase anchor proteins1 1Edited by P. E. WrightJournal of Molecular Biology, 2001
- Phosphorylated seryl and threonyl, but not tyrosyl, residues are efficient specificity determinants for GSK‐3β and ShaggyFEBS Letters, 1999
- Three-dimensional structure of the tyrosine kinase c-SrcNature, 1997
- Crystal Structure of the Human Cell Cycle Protein CksHs1: Single Domain Fold with Similarity to Kinase N-lobe DomainJournal of Molecular Biology, 1995
- Catalytic specificity of protein-tyrosine kinases is critical for selective signallingNature, 1995
- Use of an oriented peptide library to determine the optimal substrates of protein kinasesCurrent Biology, 1994
- Phosphorylated synthetic peptides as tools for studying protein phosphatasesBiochimica et Biophysica Acta (BBA) - Molecular Cell Research, 1994