Peptide mini-scaffold facilitates JNK3 activation in cells

Three-kinase mitogen-activated protein kinase (MAPK) signaling cascades are present in virtually all eukaryotic cells. MAPK cascades are organized by scaffold proteins, which assemble cognate kinases into productive signaling complexes. Arrestin-3 facilitates JNK activation in cells, and a short 25-...

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Published inScientific reports Vol. 6; no. 1; p. 21025
Main Authors Zhan, Xuanzhi, Stoy, Henriette, Kaoud, Tamer S., Perry, Nicole A., Chen, Qiuyan, Perez, Alejandro, Els-Heindl, Sylvia, Slagis, Jack V., Iverson, Tina M., Beck-Sickinger, Annette G., Gurevich, Eugenia V., Dalby, Kevin N., Gurevich, Vsevolod V.
Format Journal Article
LanguageEnglish
Published London Nature Publishing Group UK 12.02.2016
Nature Publishing Group
Subjects
13/106
13/109
13/95
631/45/612/194
631/80/86/2363
82/83
96/95
Animals
Arrestin
beta-Arrestin 1 - chemistry
beta-Arrestin 2 - chemistry
Cercopithecus aethiops
COS Cells
Enzyme Activation - drug effects
Enzyme Activators - chemical synthesis
Enzyme Activators - chemistry
Enzyme Activators - pharmacology
Humanities and Social Sciences
Humans
JNK protein
JNK3 protein
Kinases
MAP kinase
Mitogen-Activated Protein Kinase 10 - genetics
Mitogen-Activated Protein Kinase 10 - metabolism
multidisciplinary
Peptides
Peptides - chemical synthesis
Peptides - chemistry
Peptides - pharmacology
Protein kinase
Science
Science (multidisciplinary)
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Summary:Three-kinase mitogen-activated protein kinase (MAPK) signaling cascades are present in virtually all eukaryotic cells. MAPK cascades are organized by scaffold proteins, which assemble cognate kinases into productive signaling complexes. Arrestin-3 facilitates JNK activation in cells, and a short 25-residue arrestin-3 peptide was identified as the critical JNK3-binding element. Here we demonstrate that this peptide also binds MKK4, MKK7, and ASK1, which are upstream JNK3-activating kinases. This peptide is sufficient to enhance JNK3 activity in cells. A homologous arrestin-2 peptide, which differs only in four positions, binds MKK4, but not MKK7 or JNK3, and is ineffective in cells at enhancing activation of JNK3. The arrestin-3 peptide is the smallest MAPK scaffold known. This peptide or its mimics can regulate MAPKs, affecting cellular decisions to live or die.
Bibliography:ObjectType-Article-1
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Present address: Department of Chemistry, Tennessee Tech University, P.O. Box 5055, Cookeville, TN 38505.
ISSN:2045-2322
2045-2322
DOI:10.1038/srep21025