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Peptide mini-scaffold facilitates JNK3 activation in cells

Article scientifique 2016 Anglais

Résumé

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.

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Zhan, X., Stoy, H., Kaoud, T., Perry, N., Chen, Q., Pérez, A., Els‐Heindl, S., Slagis, J., Iverson, T., Beck‐Sickinger, A., Gurevich, E., Dalby, K., Gurevich, V. (2016). Peptide mini-scaffold facilitates JNK3 activation in cells. https://doi.org/10.1038/srep21025

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Auteur(s)

Xuanzhi Zhan Henriette Stoy Tamer S. Kaoud Nicole A. Perry Qiuyan Chen Alejandro Pérez Sylvia Els‐Heindl Jack V. Slagis T.M. Iverson Annette G. Beck‐Sickinger Eugenia V. Gurevich Kevin N. Dalby Vsevolod V. Gurevich

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