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Human Interaction Network Ontology
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Edited: Shamovsky, V, 2010-02-27 Reviewed: Gillespie, ME, 2010-02-27 Human p38 MAPK alpha forms a complex with MK2 even when the signaling pathway is not activated. This heterodimer is found mainly in the nucleus. The crystal structure of the unphosphorylated p38alpha-MK2 heterodimer was determined. The C-terminal regulatory domain of MK2 binds in the docking groove of p38 MAPK alpha, and the ATP-binding sites of both kinases are at the heterodimer interface.<p>Upon activation, p38 MAPK alpha activates MK2 by phosphorylating Thr-222, Ser-272, and Thr-334. <p>The phosphorylation of MK2 at Thr-334 attenuates the affinity of the binary complex MK2:p38 alpha by an order of magnitude and leads to a large conformational change of an autoinhibitory domain in MK2. This conformational change unmasks not only the MK2 substrate-binding site but also the MK2 nuclear export signal (NES) thus leading to the MK2:p38 alpha translocation from the nucleus to the cytoplasm. Cytoplasmic, active MK2 then phosphorylates downstream targets such as the heat-shock protein HSP27 and tristetraprolin (TTP).<p>MAPKAPK (MAPK-activated protein) kinase 3 (MK3, also known as 3pK) has been identified as the second p38 MAPK-activated kinase that is stimulated by different stresses (McLaughlin et al. 1996; Sithanandam et al. 1996; reviewed in Gaestel 2006). MK3 shows 75% sequence identity to MK2 and, like MK2, is activated by p38 MAPK alpha and p38 MAPK beta. MK3 phosphorylates peptide substrates with kinetic constants similar to MK2 and phosphorylates the same serine residues in HSP27 at the same relative rates as MK2 (Clifton et al. 1996) indicating an identical phosphorylation-site consensus sequence. Hence, it is assumed that its substrate spectrum is either identical to or at least overlapping with MK2. has a Stoichiometric coefficient of 3 Authored: Shamovsky, V, 2009-12-16 |
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http://purl.obolibrary.org/obo/HINO_0026425 |
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Edited: Shamovsky, V, 2010-02-27 Reviewed: Gillespie, ME, 2010-02-27 Human p38 MAPK alpha forms a complex with MK2 even when the signaling pathway is not activated. This heterodimer is found mainly in the nucleus. The crystal structure of the unphosphorylated p38alpha-MK2 heterodimer was determined. The C-terminal regulatory domain of MK2 binds in the docking groove of p38 MAPK alpha, and the ATP-binding sites of both kinases are at the heterodimer interface.<p>Upon activation, p38 MAPK alpha activates MK2 by phosphorylating Thr-222, Ser-272, and Thr-334. <p>The phosphorylation of MK2 at Thr-334 attenuates the affinity of the binary complex MK2:p38 alpha by an order of magnitude and leads to a large conformational change of an autoinhibitory domain in MK2. This conformational change unmasks not only the MK2 substrate-binding site but also the MK2 nuclear export signal (NES) thus leading to the MK2:p38 alpha translocation from the nucleus to the cytoplasm. Cytoplasmic, active MK2 then phosphorylates downstream targets such as the heat-shock protein HSP27 and tristetraprolin (TTP).<p>MAPKAPK (MAPK-activated protein) kinase 3 (MK3, also known as 3pK) has been identified as the second p38 MAPK-activated kinase that is stimulated by different stresses (McLaughlin et al. 1996; Sithanandam et al. 1996; reviewed in Gaestel 2006). MK3 shows 75% sequence identity to MK2 and, like MK2, is activated by p38 MAPK alpha and p38 MAPK beta. MK3 phosphorylates peptide substrates with kinetic constants similar to MK2 and phosphorylates the same serine residues in HSP27 at the same relative rates as MK2 (Clifton et al. 1996) indicating an identical phosphorylation-site consensus sequence. Hence, it is assumed that its substrate spectrum is either identical to or at least overlapping with MK2. has a Stoichiometric coefficient of 3 Authored: Shamovsky, V, 2009-12-16
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Pubmed17255097 Pubmed12171911 Pubmed17395714 Reactome, http://www.reactome.org Pubmed15287722 Pubmed8846784
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Active p38 MAPK phosphorylates MAPKAPK2 or 3
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HINO:0026425
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Reactome Database ID Release 43450222 ReactomeREACT_21375 EC Number: 2.7.11
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