Peptide mini-scaffold facilitates JNK3 activation in cells

• DOI: 10.1038/srep21025
• Publication Date: 2016-02-12T10:57:16Z
• Authors: Xuanzhi Zhan; Henriette Stoy; Tamer S. Kaoud; Nicole A. Perry; Qiuyan Chen; Alejandro Perez; Sylvia Els-Heindl; Jack V. Slagis; Tina M. Iverson; Annette G. Beck-S...; Eugenia V. Gurevich; Kevin N. Dalby; Vsevolod V. Gurevich
• Keywords: 0303 health sciences; Enzyme Activators; beta-Arrestin 2; Article; Enzyme Activation; 03 medical and health sciences; beta-Arrestin 1; Mitogen-Activated Protein Kinase 10; COS Cells; Chlorocebus aethiops; Animals; Humans; Peptides

AbstractThree-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.