Structural Insight into the 14-3-3 Protein-dependent Inhibition of Protein Kinase ASK1 (Apoptosis Signal-regulating kinase 1)

Result code in IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F67985823%3A_____%2F16%3A00464968" target="_blank" >RIV/67985823:_____/16:00464968 - isvavai.cz</a>

Alternative codes found

RIV/61388971:_____/16:00464968 RIV/00216208:11320/16:10332109 RIV/00216208:11310/16:10332109

Result on the web

<a href="http://dx.doi.org/10.1074/jbc.M116.724310" target="_blank" >http://dx.doi.org/10.1074/jbc.M116.724310</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1074/jbc.M116.724310" target="_blank" >10.1074/jbc.M116.724310</a>

Result language

angličtina

Original language name

Structural Insight into the 14-3-3 Protein-dependent Inhibition of Protein Kinase ASK1 (Apoptosis Signal-regulating kinase 1)

Original language description

Apoptosis signal-regulating kinase 1 (ASK1, also known as MAP3K5), a member of the mitogen-activated protein kinase kinase kinase (MAP3K) family, regulates diverse physiological processes. The activity of ASK1 is triggered by various stress stimuli and is involved in the pathogenesis of cancer, neurodegeneration, inflammation, and diabetes. ASK1 forms a high molecular mass complex whose activity is, under non-stress conditions, suppressed through interaction with thioredoxin and the scaffolding protein 14-3-3. The 14-3-3 protein binds to the phosphorylated Ser-966 motif downstream of the ASK1 kinase domain. The role of 14-3-3 in the inhibition of ASK1 has yet to be elucidated. In this study we performed structural analysis of the complex between the ASK1 kinase domain phosphorylated at Ser-966 (pASK1-CD) and the 14-3-3 protein. Small angle x-ray scattering (SAXS) measurements and chemical cross-linking revealed that the pASK1-CD14-3-3 complex is dynamic and conformationally heterogeneous. In addition, structural analysis coupled with the results of phosphorus NMR and time-resolved tryptophan fluorescence measurements suggest that 14-3-3 interacts with the kinase domain of ASK1 in close proximity to its active site, thus indicating this interaction might block its accessibility and/or affect its conformation.

Czech name

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Czech description

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Type

J_x - Unclassified - Peer-reviewed scientific article (Jimp, Jsc and Jost)

CEP classification

CE - Biochemistry

OECD FORD branch

—

Project

<a href="/en/project/GA14-10061S" target="_blank" >GA14-10061S: Regulatory mechanism of kinase activity of protein kinase ASK1</a><br>

Continuities

I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Publication year

2016

Confidentiality

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Name of the periodical

Journal of Biological Chemistry

ISSN

0021-9258

e-ISSN

—

Volume of the periodical

291

Issue of the periodical within the volume

39

Country of publishing house

US - UNITED STATES

Number of pages

13

Pages from-to

20753-20765

UT code for WoS article

000384574800036

EID of the result in the Scopus database

2-s2.0-84988565725