Cited by 62Protein Kinase Regulation and GTPase SignalingProtein Tyrosine PhosphatasesEnzyme Structure and Function

Catalytically Active MAP KAP Kinase 2 Structures in Complex with Staurosporine and ADP Reveal Differences with the Autoinhibited Enzyme

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Underwood, Kathryn W., Parris, Kevin D., Federico, Elizabeth, Mosyak, Lidia, Czerwinski, Robert M., Shane, Tania, Taylor, Meggin, Svenson, Kristine +11 more·2003·Structure

Abstract

MAP KAP kinase 2 (MK2), a Ser/Thr kinase, plays a crucial role in the inflammatory process. We have determined the crystal structures of a catalytically active C-terminal deletion form of human MK2, residues 41-364, in complex with staurosporine at 2.7 A and with ADP at 3.2 A, revealing overall structural similarity with other Ser/Thr kinases. Kinetic analysis reveals that the K(m) for ATP is very similar for MK2 41-364 and p38-activated MK2 41-400. Conversely, the catalytic rate and binding for peptide substrate are dramatically reduced in MK2 41-364. However, phosphorylation of MK2 41-364 by p38 restores the V(max) and K(m) for peptide substrate to values comparable to those seen in p38-activated MK2 41-400, suggesting a mechanism for regulation of enzyme activity.

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Crossref · 10.1016/s0969-2126(03)00092-3

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Authors
Underwood, K. W., Parris, K. D., Federico, E., Mosyak, L., Czerwinski, R. M., Shane, T., Taylor, M., Svenson, K., Liu, Y., Hsiao, C.-L., Wolfrom, S., Maguire, M., Malakian, K., Telliez, J.-B., Lin, L.-L., Kriz, R. W., Seehra, J., Somers, W. S., & Stahl, M. L.
Affiliations
Wyeth (US)
Corresponding author
  • Underwood, Kathryn W.
  • Parris, Kevin D.
Venue
Structure
Publisher
Elsevier BV
Published
2003-06
Volume
11
Issue
6
Pages
627-636
ISSN
0969-2126 (ISSN-L)
OpenAlex
W2034611095
Cited by
62
References
39
Citations by year
2025: 1 · 2023: 2 · 2019: 1 · 2018: 1 · 2017: 1 · 2016: 2 · 2015: 3 · 2014: 5 · 2013: 2 · 2012: 5
FWCI
1.71
Type
journal article
Language
en
Open access
Locations
  • Structure (publishedVersion)
  • PubMed (publishedVersion)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Kinase Regulation and GTPase Signaling
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Tyrosine Phosphatases
  • Physical Sciences › Materials Science › Materials Chemistry › Enzyme Structure and Function
Keywords
MAPKAPK2, staurosporine, ADP, Ser/Thr kinase, p38 MAPK, kinase activation, peptide substrate binding, C-terminal deletion mutants, inflammatory signaling, kinase crystal structure
MeSH terms
MAP-Kinase-Activated Kinase 2, Adenosine Diphosphate, Amino Acid Sequence, Enzyme Activation, Humans, Models, Molecular, Molecular Sequence Data, Phosphorylation, Molecular Structure, Sequence Alignment, Protein Serine-Threonine Kinases, Protein Structure, Tertiary, Staurosporine, Mitogen-Activated Protein Kinases, Macromolecular Substances, Intracellular Signaling Peptides and Proteins, p38 Mitogen-Activated Protein Kinases

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