14-3-3 proteins interact with specific MEK kinases

Détails

ID Serval
serval:BIB_F91F6D7E1C28
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Titre
14-3-3 proteins interact with specific MEK kinases
Périodique
Journal of Biological Chemistry
Auteur(s)
Fanger  G. R., Widmann  C., Porter  A. C., Sather  S., Johnson  G. L., Vaillancourt  R. R.
ISSN
0021-9258 (Print)
Statut éditorial
Publié
Date de publication
02/1998
Volume
273
Numéro
6
Pages
3476-83
Notes
Journal Article
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, P.H.S. --- Old month value: Feb 6
Résumé
MEK (mitogen-activated protein kinase/extracellular signal-regulated kinase kinase) kinases (MEKKs) regulate c-Jun N-terminal kinase and extracellular response kinase pathways. The 14-3-3zeta and 14-3-3epsilon isoforms were isolated in a two-hybrid screen for proteins interacting with the N-terminal regulatory domain of MEKK3. 14-3-3 proteins bound both the N-terminal regulatory and C-terminal kinase domains of MEKK3. The binding affinity of 14-3-3 for the MEKK3 N terminus was 90 nM, demonstrating a high affinity interaction. 14-3-3 proteins also interacted with MEKK1 and MEKK2, but not MEKK4. Endogenous 14-3-3 protein and MEKK1 and MEKK2 were similarly distributed in the cell, consistent with their in vitro interactions. MEKK1 and 14-3-3 proteins colocalized using two-color digital confocal immunofluorescence. Binding of 14-3-3 proteins mapped to the N-terminal 393 residues of 196-kDa MEKK1. Unlike MEKK2 and MEKK3, the C-terminal kinase domain of MEKK1 demonstrated little or no ability to interact with 14-3-3 proteins. MEKK1, but not MEKK2, -3 or -4, is a caspase-3 substrate that when cleaved releases the kinase domain from the N-terminal regulatory domain. Functionally, caspase-3 cleavage of MEKK1 releases the kinase domain from the N-terminal 14-3-3-binding region, demonstrating that caspases can selectively alter protein kinase interactions with regulatory proteins. With regard to MEKK1, -2 and -3, 14-3-3 proteins do not appear to directly influence activity, but rather function as "scaffolds" for protein-protein interactions.
Mots-clé
14-3-3 Proteins Animals COS Cells Microscopy, Confocal Microscopy, Fluorescence Protein Binding Protein-Serine-Threonine Kinases/genetics/*metabolism Proteins/*metabolism Recombinant Proteins/genetics/metabolism Saccharomyces cerevisiae/genetics Subcellular Fractions/metabolism *Tyrosine 3-Monooxygenase
Pubmed
Web of science
Open Access
Oui
Création de la notice
24/01/2008 15:43
Dernière modification de la notice
20/08/2019 17:24
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