Modular structure of a docking surface on MAPK phosphatases
- PMID: 11953434
- DOI: 10.1074/jbc.M202096200
Modular structure of a docking surface on MAPK phosphatases
Abstract
Mitogen-activated protein kinases (MAPKs) must be precisely inactivated to achieve proper functions in the cells. Ten members of dual specificity phosphatases specifically acting on MAPKs, termed MAPK phosphatases (MKPs), have been reported. Each member has its own substrate specificity that should be tightly regulated. However, the molecular mechanism underlying the regulation of the specificity is largely unknown. In the MAPK signaling pathways, docking interactions, which are different from transient enzyme-substrate interaction, are known to regulate the enzymatic specificity. Here we have identified and characterized a docking surface of MKPs. Our results show that a docking surface is composed of a tandem alignment of three subregions (modules): a cluster of positively charged amino acids, a cluster of hydrophobic amino acids, and a cluster of positively charged amino acids (positive-hydrophobic-positive). This modular structure well fits the docking groove on MAPKs that we have previously identified and may contribute to regulating the docking specificity of the MKP family. The position, number, and species of charged amino acids in each module including the central hydrophobic subregion are important factors in regulation of docking to specific MAPKs. This modular structure in the docking interaction may define a novel model of protein-protein interaction that would also regulate other systems.
Similar articles
-
Distinct binding determinants for ERK2/p38alpha and JNK map kinases mediate catalytic activation and substrate selectivity of map kinase phosphatase-1.J Biol Chem. 2001 May 11;276(19):16491-500. doi: 10.1074/jbc.M010966200. Epub 2001 Jan 30. J Biol Chem. 2001. PMID: 11278799
-
A Novel MAPK phosphatase MKP-7 acts preferentially on JNK/SAPK and p38 alpha and beta MAPKs.J Biol Chem. 2001 Jul 13;276(28):26629-39. doi: 10.1074/jbc.M101981200. Epub 2001 May 18. J Biol Chem. 2001. PMID: 11359773
-
MKP-7, a novel mitogen-activated protein kinase phosphatase, functions as a shuttle protein.J Biol Chem. 2001 Oct 19;276(42):39002-11. doi: 10.1074/jbc.M104600200. Epub 2001 Aug 6. J Biol Chem. 2001. PMID: 11489891
-
Diverse physiological functions for dual-specificity MAP kinase phosphatases.J Cell Sci. 2006 Nov 15;119(Pt 22):4607-15. doi: 10.1242/jcs.03266. J Cell Sci. 2006. PMID: 17093265 Review.
-
MAPK phosphatases--regulating the immune response.Nat Rev Immunol. 2007 Mar;7(3):202-12. doi: 10.1038/nri2035. Nat Rev Immunol. 2007. PMID: 17318231 Review.
Cited by
-
The Phosphatase Dusp7 Drives Meiotic Resumption and Chromosome Alignment in Mouse Oocytes.Cell Rep. 2016 Oct 25;17(5):1426-1437. doi: 10.1016/j.celrep.2016.10.007. Cell Rep. 2016. PMID: 27783954 Free PMC article.
-
A semidominant mutation in an Arabidopsis mitogen-activated protein kinase phosphatase-like gene compromises cortical microtubule organization.Plant Cell. 2004 Jul;16(7):1841-53. doi: 10.1105/tpc.021865. Epub 2004 Jun 18. Plant Cell. 2004. PMID: 15208393 Free PMC article.
-
Dual-specificity MAP kinase phosphatases (MKPs): shaping the outcome of MAP kinase signalling.FEBS J. 2013 Jan;280(2):489-504. doi: 10.1111/j.1742-4658.2012.08716.x. Epub 2012 Aug 28. FEBS J. 2013. PMID: 22812510 Free PMC article. Review.
-
Spatiotemporal regulation of ERK2 by dual specificity phosphatases.J Biol Chem. 2008 Sep 26;283(39):26612-23. doi: 10.1074/jbc.M801500200. Epub 2008 Jul 23. J Biol Chem. 2008. PMID: 18650424 Free PMC article.
-
Acetylation of mitogen-activated protein kinase phosphatase-1 inhibits Toll-like receptor signaling.J Exp Med. 2008 Jun 9;205(6):1491-503. doi: 10.1084/jem.20071728. Epub 2008 May 26. J Exp Med. 2008. PMID: 18504304 Free PMC article.
Publication types
MeSH terms
Substances
LinkOut - more resources
Full Text Sources
Miscellaneous
