Journal
PROTEIN SCIENCE
Volume 22, Issue 12, Pages 1698-1710Publisher
WILEY
DOI: 10.1002/pro.2374
Keywords
MAP kinase; ERK; p38; JNK; structure; kinase interaction motif; KIM; D-motif; NMR; SAXS; PTP; DUSP
Categories
Funding
- American Cancer Society [RSG-08-067-01-LIB]
- National Institute of Health [R01GM098482, R01GM100910]
Ask authors/readers for more resources
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.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available