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PDBsum entry 1kwp
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Contents |
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* Residue conservation analysis
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References listed in PDB file
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Key reference
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Title
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Structure of mitogen-Activated protein kinase-Activated protein (mapkap) kinase 2 suggests a bifunctional switch that couples kinase activation with nuclear export.
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Authors
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W.Meng,
L.L.Swenson,
M.J.Fitzgibbon,
K.Hayakawa,
E.Ter haar,
A.E.Behrens,
J.R.Fulghum,
J.A.Lippke.
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Ref.
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J Biol Chem, 2002,
277,
37401-37405.
[DOI no: ]
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PubMed id
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Abstract
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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.
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Figure 1.
Fig. 1. Ribbon diagram of the MAPKAPK2 structure. The
N-lobe of the kinase domain is colored light blue. The C-lobe of
the kinase domain is colored dark blue. The regulatory domain is
colored red. The key regulatory residue threonine 334 is
labeled. The dotted line indicates the missing part of
activation loop.
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Figure 5.
Fig. 5. Interaction between the kinase domain C-lobe and
the C-terminal regulatory domain second helix of MAPKAPK2.
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The above figures are
reprinted
by permission from the ASBMB:
J Biol Chem
(2002,
277,
37401-37405)
copyright 2002.
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