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Peptide mini-scaffold facilitates JNK3 activation in cells.

ABSTRACT: 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.

SUBMITTER: Zhan X

PROVIDER: S-EPMC4751492 | biostudies-literature | 2016 Feb

REPOSITORIES: biostudies-literature

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Peptide mini-scaffold facilitates JNK3 activation in cells.

Zhan Xuanzhi X Stoy Henriette H Kaoud Tamer S TS Perry Nicole A NA Chen Qiuyan Q Perez Alejandro A Els-Heindl Sylvia S Slagis Jack V JV Iverson Tina M TM Beck-Sickinger Annette G AG Gurevich Eugenia V EV Dalby Kevin N KN Gurevich Vsevolod V VV

Scientific reports 20160212

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 ...[more]

PMID: 26868142

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