1KWP

Crystal Structure of MAPKAP2

Summary for 1KWP

• Entry DOI: 10.2210/pdb1kwp/pdb
• Descriptor: MAP Kinase Activated Protein Kinase 2, MERCURY (II) ION (3 entities in total)
• Functional Keywords: mapkap2, protein kinase, signal transduction, transferase
• Biological source: Homo sapiens (human)
• Total number of polymer chains: 2
• Total formula weight: 94067.74

Authors

Meng, W.,Swenson, L.L.,Fitzgibbon, M.J.,Hayakawa, K.,ter Haar, E.,Behrens, A.E.,Fulghum, J.R.,Lippke, J.A. (deposition date: 2002-01-30, release date: 2002-09-18, Last modification date: 2024-02-14)

Primary citation

Meng, W.,Swenson, L.L.,Fitzgibbon, M.J.,Hayakawa, K.,Ter Haar, E.,Behrens, A.E.,Fulghum, J.R.,Lippke, J.A.
Structure of Mitogen-activated Protein Kinase-activated Protein (MAPKAP) Kinase 2 Suggests a Bifunctional Switch That Couples Kinase Activation with Nuclear Export
J.Biol.Chem., 277:37401-37405, 2002

PubMed Abstract: 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.

PubMed: 12171911
DOI: 10.1074/jbc.C200418200

Experimental method

X-RAY DIFFRACTION (2.8 Å)