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'''Crystal Structure of MAPKAP2''' | '''Crystal Structure of MAPKAP2''' | ||
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[[Category: Meng, W.]] | [[Category: Meng, W.]] | ||
[[Category: Swenson, L L.]] | [[Category: Swenson, L L.]] | ||
[[Category: | [[Category: Crystallography]] | ||
[[Category: | [[Category: Mapkap2]] | ||
[[Category: | [[Category: Protein kinase]] | ||
[[Category: | [[Category: Signal transduction]] | ||
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Revision as of 20:15, 2 May 2008
Crystal Structure of MAPKAP2
Overview
MAPK-activated protein kinase 2 (MAPKAPK2), one of several kinases directly phosphorylated and activated by p38 MAPK, plays a central role in the inflammatory response. The activated MAPKAPK2 phosphorylates its nuclear targets CREB/ATF1, serum response factor, and E2A protein E47 and its cytoplasmic targets HSP25/27, LSP-1, 5-lipoxygenase, glycogen synthase, and tyrosine hydroxylase. The crystal structure of unphosphorylated MAPKAPK2, determined at 2.8 A resolution, includes the kinase domain and the C-terminal regulatory domain. Although the protein is inactive, the kinase domain adopts an active conformation with aspartate 366 mimicking the missing phosphorylated threonine 222 in the activation loop. The C-terminal regulatory domain forms a helix-turn-helix plus a long strand. Phosphorylation of threonine 334, which is located between the kinase domain and the C-terminal regulatory domain, may serve as a switch for MAPKAPK2 nuclear import and export. Phosphorylated MAPKAPK2 masks the nuclear localization signal at its C terminus by binding to p38. It unmasks the nuclear export signal, which is part of the second C-terminal helix packed along the surface of kinase domain C-lobe, and thereby carries p38 to the cytoplasm.
About this Structure
1KWP is a Single protein structure of sequence from Homo sapiens. Full crystallographic information is available from OCA.
Reference
Structure of mitogen-activated protein kinase-activated protein (MAPKAP) kinase 2 suggests a bifunctional switch that couples kinase activation with nuclear export., Meng W, Swenson LL, Fitzgibbon MJ, Hayakawa K, Ter Haar E, Behrens AE, Fulghum JR, Lippke JA, J Biol Chem. 2002 Oct 4;277(40):37401-5. Epub 2002 Aug 8. PMID:12171911 Page seeded by OCA on Fri May 2 23:15:50 2008