title: 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.
authors: Departments of Pharmacology, Vanderbilt University, Nashville, TN 37232, USA.
authors: Xuanzhi
authors: X
authors: Zhan
authors: Departments of Pharmacology, Vanderbilt University, Nashville, TN 37232, USA.|University of Tübingen, Tübingen 72074, Germany.
authors: Henriette
authors: H
authors: Stoy
authors: Faculty of Pharmacy, Minia University, Minia, Egypt.|Division of Medicinal Chemistry, The University of Texas at Austin, Austin, Texas 78712, USA.
authors: Tamer S
authors: TS
authors: Kaoud
authors: Departments of Pharmacology, Vanderbilt University, Nashville, TN 37232, USA.
authors: Nicole A
authors: NA
authors: Perry
authors: Departments of Pharmacology, Vanderbilt University, Nashville, TN 37232, USA.
authors: Qiuyan
authors: Q
authors: Chen
authors: Departments of Pharmacology, Vanderbilt University, Nashville, TN 37232, USA.
authors: Alejandro
authors: A
authors: Perez
authors: Universität Leipzig, Faculty of Biosciences, Pharmacy and Psychology, Institute of Biochemistry, Brüderstrasse 34, 04103 Leipzig, Germany.
authors: Sylvia
authors: S
authors: Els-Heindl
authors: Departments of Pharmacology, Vanderbilt University, Nashville, TN 37232, USA.
authors: Jack V
authors: JV
authors: Slagis
authors: Departments of Pharmacology, Vanderbilt University, Nashville, TN 37232, USA.|Departments of Biochemistry, Vanderbilt University, Nashville, TN 37232, USA.|Center for Structural Biology, Vanderbilt University, Nashville, TN 37232, USA.|Vanderbilt Institute of Chemical Biology, Vanderbilt University, Nashville, TN 37232, USA.
authors: Tina M
authors: TM
authors: Iverson
authors: Universität Leipzig, Faculty of Biosciences, Pharmacy and Psychology, Institute of Biochemistry, Brüderstrasse 34, 04103 Leipzig, Germany.
authors: Annette G
authors: AG
authors: Beck-Sickinger
authors: Departments of Pharmacology, Vanderbilt University, Nashville, TN 37232, USA.
authors: Eugenia V
authors: EV
authors: Gurevich
authors: Division of Medicinal Chemistry, The University of Texas at Austin, Austin, Texas 78712, USA.
authors: Kevin N
authors: KN
authors: Dalby
authors: Departments of Pharmacology, Vanderbilt University, Nashville, TN 37232, USA.
authors: Vsevolod V
authors: VV
authors: Gurevich
mesh_terms: D000818:Animals; D019556:COS Cells; D002522:Chlorocebus aethiops; D004789:Enzyme Activation / Q000187:drug effects; D020536:Enzyme Activators / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D006801:Humans; D048057:Mitogen-Activated Protein Kinase 10 / Q000235:genetics / Q000378:metabolism*; D010455:Peptides / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D000071559:beta-Arrestin 1 / Q000737:chemistry*; D000071560:beta-Arrestin 2 / Q000737:chemistry*
chemical_list: D020536:Enzyme Activators; D010455:Peptides; D000071559:beta-Arrestin 1; D000071560:beta-Arrestin 2; D048057:Mitogen-Activated Protein Kinase 10