Short Arrestin-3-Derived Peptides Activate JNK3 in Cells.
Int J Mol Sci
; 23(15)2022 Aug 04.
Article
en En
| MEDLINE
| ID: mdl-35955810
ABSTRACT
Arrestins were first discovered as suppressors of G protein-mediated signaling by G protein-coupled receptors. It was later demonstrated that arrestins also initiate several signaling branches, including mitogen-activated protein kinase cascades. Arrestin-3-dependent activation of the JNK family can be recapitulated with peptide fragments, which are monofunctional elements distilled from this multi-functional arrestin protein. Here, we use maltose-binding protein fusions of arrestin-3-derived peptides to identify arrestin elements that bind kinases of the ASK1-MKK4/7-JNK3 cascade and the shortest peptide facilitating JNK signaling. We identified a 16-residue arrestin-3-derived peptide expressed as a Venus fusion that leads to activation of JNK3α2 in cells. The strength of the binding to the kinases does not correlate with peptide activity. The ASK1-MKK4/7-JNK3 cascade has been implicated in neuronal apoptosis. While inhibitors of MAP kinases exist, short peptides are the first small molecule tools that can activate MAP kinases.
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Base de datos:
MEDLINE
Asunto principal:
Arrestina
/
Proteína Quinasa 10 Activada por Mitógenos
Idioma:
En
Revista:
Int J Mol Sci
Año:
2022
Tipo del documento:
Article