2gph

Docking motif interactions in the MAP kinase ERK2Docking motif interactions in the MAP kinase ERK2

Structural highlights

2gph is a 2 chain structure with sequence from Homo sapiens and Rattus norvegicus. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:	X-ray diffraction, Resolution 1.9Å
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

PTN7_HUMAN Protein phosphatase that acts preferentially on tyrosine-phosphorylated MAPK1. Plays a role in the regulation of T and B-lymphocyte development and signal transduction.^[1] ^[2] ^[3] ^[4] ^[5] ^[6]

Evolutionary Conservation

Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.

Publication Abstract from PubMed

MAP kinases bind activating kinases, phosphatases, and substrates through docking interactions. Here, we report a 1.9 A crystallographic analysis of inactive ERK2 bound to a "D motif" docking peptide (pepHePTP) derived from hematopoietic tyrosine phosphatase, a negative regulator of ERK2. In this complex, the complete D motif interaction defined by mutagenic analysis is observed, including extensive electrostatic interactions with the "CD" site of the kinase. Large conformational changes occur in the activation loop where the dual phosphorylation sites, which are buried in the inactive form of ERK2, become exposed to solvent in the complex. Similar conformational changes occur in a complex between ERK2 and a MEK2 (MAP/ERK kinase-2)-derived D motif peptide (pepMEK2). D motif peptides are known to bind homologous loci in the MAP kinases p38alpha and JNK1, also inducing conformational changes in these enzymes. However, the binding interactions and conformational changes are unique to each, thus contributing to specificity among MAP kinases.

Docking interactions induce exposure of activation loop in the MAP kinase ERK2.,Zhou T, Sun L, Humphreys J, Goldsmith EJ Structure. 2006 Jun;14(6):1011-9. PMID:16765894^[7]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

↑ Adachi M, Sekiya M, Isobe M, Kumura Y, Ogita Z, Hinoda Y, Imai K, Yachi A. Molecular cloning and chromosomal mapping of a human protein-tyrosine phosphatase LC-PTP. Biochem Biophys Res Commun. 1992 Aug 14;186(3):1607-15. PMID:1510684
↑ Zanke B, Suzuki H, Kishihara K, Mizzen L, Minden M, Pawson A, Mak TW. Cloning and expression of an inducible lymphoid-specific, protein tyrosine phosphatase (HePTPase). Eur J Immunol. 1992 Jan;22(1):235-9. PMID:1530918 doi:http://dx.doi.org/10.1002/eji.1830220134
↑ Saxena M, Williams S, Gilman J, Mustelin T. Negative regulation of T cell antigen receptor signal transduction by hematopoietic tyrosine phosphatase (HePTP). J Biol Chem. 1998 Jun 19;273(25):15340-4. PMID:9624114
↑ Saxena M, Williams S, Brockdorff J, Gilman J, Mustelin T. Inhibition of T cell signaling by mitogen-activated protein kinase-targeted hematopoietic tyrosine phosphatase (HePTP). J Biol Chem. 1999 Apr 23;274(17):11693-700. PMID:10206983
↑ Saxena M, Williams S, Tasken K, Mustelin T. Crosstalk between cAMP-dependent kinase and MAP kinase through a protein tyrosine phosphatase. Nat Cell Biol. 1999 Sep;1(5):305-11. PMID:10559944 doi:http://dx.doi.org/10.1038/13024
↑ Pettiford SM, Herbst R. The MAP-kinase ERK2 is a specific substrate of the protein tyrosine phosphatase HePTP. Oncogene. 2000 Feb 17;19(7):858-69. PMID:10702794 doi:http://dx.doi.org/10.1038/sj.onc.1203408
↑ Zhou T, Sun L, Humphreys J, Goldsmith EJ. Docking interactions induce exposure of activation loop in the MAP kinase ERK2. Structure. 2006 Jun;14(6):1011-9. PMID:16765894 doi:10.1016/j.str.2006.04.006

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OCA

[1] Adachi M, Sekiya M, Isobe M, Kumura Y, Ogita Z, Hinoda Y, Imai K, Yachi A. Molecular cloning and chromosomal mapping of a human protein-tyrosine phosphatase LC-PTP. Biochem Biophys Res Commun. 1992 Aug 14;186(3):1607-15. PMID:1510684

[2] Zanke B, Suzuki H, Kishihara K, Mizzen L, Minden M, Pawson A, Mak TW. Cloning and expression of an inducible lymphoid-specific, protein tyrosine phosphatase (HePTPase). Eur J Immunol. 1992 Jan;22(1):235-9. PMID:1530918 doi:http://dx.doi.org/10.1002/eji.1830220134

[3] Saxena M, Williams S, Gilman J, Mustelin T. Negative regulation of T cell antigen receptor signal transduction by hematopoietic tyrosine phosphatase (HePTP). J Biol Chem. 1998 Jun 19;273(25):15340-4. PMID:9624114

[4] Saxena M, Williams S, Brockdorff J, Gilman J, Mustelin T. Inhibition of T cell signaling by mitogen-activated protein kinase-targeted hematopoietic tyrosine phosphatase (HePTP). J Biol Chem. 1999 Apr 23;274(17):11693-700. PMID:10206983

[5] Saxena M, Williams S, Tasken K, Mustelin T. Crosstalk between cAMP-dependent kinase and MAP kinase through a protein tyrosine phosphatase. Nat Cell Biol. 1999 Sep;1(5):305-11. PMID:10559944 doi:http://dx.doi.org/10.1038/13024

[6] Pettiford SM, Herbst R. The MAP-kinase ERK2 is a specific substrate of the protein tyrosine phosphatase HePTP. Oncogene. 2000 Feb 17;19(7):858-69. PMID:10702794 doi:http://dx.doi.org/10.1038/sj.onc.1203408

[7] Zhou T, Sun L, Humphreys J, Goldsmith EJ. Docking interactions induce exposure of activation loop in the MAP kinase ERK2. Structure. 2006 Jun;14(6):1011-9. PMID:16765894 doi:10.1016/j.str.2006.04.006

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