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Protein Sci. 2013 Dec;22(12):1698-710. doi: 10.1002/pro.2374. Epub 2013 Oct 19.

Molecular basis of MAP kinase regulation.

Author information

1
Department of Molecular Pharmacology, Physiology and Biotechnology, Brown University, Providence, Rhode Island, 02912; Department of Chemistry, Brown University, Providence, Rhode Island, 02912.

Abstract

Mitogen-activated protein kinases (MAPKs; ERK1/2, p38, JNK, and ERK5) have evolved to transduce environmental and developmental signals (growth factors, stress) into adaptive and programmed responses (differentiation, inflammation, apoptosis). Almost 20 years ago, it was discovered that MAPKs contain a docking site in the C-terminal lobe that binds a conserved 13-16 amino acid sequence known as the D- or KIM-motif (kinase interaction motif). Recent crystal structures of MAPK:KIM-peptide complexes are leading to a precise understanding of how KIM sequences contribute to MAPK selectivity. In addition, new crystal and especially NMR studies are revealing how residues outside the canonical KIM motif interact with specific MAPKs and contribute further to MAPK selectivity and signaling pathway fidelity. In this review, we focus on these recent studies, with an emphasis on the use of NMR spectroscopy, isothermal titration calorimetry and small angle X-ray scattering to investigate these processes.

KEYWORDS:

D-motif; DUSP; ERK; JNK; KIM; MAP kinase; NMR; PTP; SAXS; kinase interaction motif; p38; structure

PMID:
24115095
PMCID:
PMC3843625
DOI:
10.1002/pro.2374
[Indexed for MEDLINE]
Free PMC Article

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