ERK2 shows a restrictive and locally selective mechanism of recognition by its tyrosine phosphatase inactivators not shared by its activator MEK1
| Autor: | Rafael Pulido, Wiljan Hendriks, Rocío Cejudo-Marín, Carmen Blanco-Aparicio, Jan Schepens, Lydia Tabernero, Lieke C. J. van den Berk, Pablo Rios, Céline Tárrega |
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| Rok vydání: | 2005 |
| Předmět: |
Chemical and physical biology [NCMLS 7]
endocrine system diseases MAP Kinase Kinase 1 Protein tyrosine phosphatase Biology Mitogen-activated protein kinase kinase environment and public health Biochemistry Cell Line Substrate Specificity MAP2K7 Mitogen-Activated Protein Kinase 14 Mice Cytosol Dual Specificity Phosphatase 6 Two-Hybrid System Techniques Phosphoprotein Phosphatases Animals Humans Receptor-Like Protein Tyrosine Phosphatases Class 7 c-Raf Phosphorylation Molecular Biology Mitogen-Activated Protein Kinase 1 MAP kinase kinase kinase MAPKAPK2 Cyclin-dependent kinase 2 Intracellular Signaling Peptides and Proteins Cell Biology Recombinant Proteins Enzyme Activation enzymes and coenzymes (carbohydrates) Amino Acid Substitution biology.protein Cyclin-dependent kinase 9 Protein Tyrosine Phosphatases biological phenomena cell phenomena and immunity Cellular energy metabolism [UMCN 5.3] Functional Neurogenomics [DCN 2] hormones hormone substitutes and hormone antagonists Protein Binding |
| Zdroj: | Journal of Biological Chemistry, 280, 37885-94 Journal of Biological Chemistry, 280, 45, pp. 37885-94 |
| ISSN: | 1083-351X 0021-9258 |
| Popis: | Contains fulltext : 48764.pdf (Publisher’s version ) (Open Access) The two regulatory residues that control the enzymatic activity of the mitogen-activated protein (MAP) kinase ERK2 are phosphorylated by the unique MAP kinase kinases MEK1/2 and dephosphorylated by several tyrosine-specific and dual specificity protein phosphatases. Selective docking interactions facilitate these phosphorylation and dephosphorylation events, controlling the specificity and duration of the MAP kinase activation-inactivation cycles. We have analyzed the contribution of specific residues of ERK2 in the physical and functional interaction with the ERK2 phosphatase inactivators PTP-SL and MKP-3 and with its activator MEK1. Single mutations in ERK2 that abrogated the dephosphorylation by endogenous tyrosine phosphatases from HEK293 cells still allowed efficient phosphorylation by endogenous MEK1/2. Discrete ERK2 mutations at the ERK2 docking groove differentially affected binding and inactivation by PTP-SL and MKP-3. Remarkably, the cytosolic retention of ERK2 by its activator MEK1 was not affected by any of the analyzed ERK2 single amino acid substitutions. A chimeric MEK1 protein, containing the kinase interaction motif of PTP-SL, bound tightly to ERK2 through its docking groove and behaved as a gain-of-function MAP kinase kinase that hyperactivated ERK2. Our results provide evidence that the ERK2 docking groove is more restrictive and selective for its tyrosine phosphatase inactivators than for MEK1/2 and indicate that distinct ERK2 residues modulate the docking interactions with activating and inactivating effectors. |
| Databáze: | OpenAIRE |
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