Year: 2022
Type: article
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.
DOI: 10.3390/ijms23158679
Language: English
Subfield: Molecular Biology
Domain: Life Sciences
Open Access status: gold
Estimated APC paid: $2,408
Awards: G1152651913, Arrestin-3 scaffolding of the JNK3 activation cascade as a model of arrestin-dependent signaling, Training in Pharmacological Sciences, Mechanisms of signal bias in arrestins, G4681783834, G52711424, Arrestin-3 interaction with the ASK1-MKK4/7-JNK3 cascade, G5592002047, G6010235770, G6238328371, G6555779565, G6560162726, G6795838433, G7050682148, G743847574, G7448766994, G7883404633, G8536882922, G8601620063, G8650056857, G8883367568, G9000071520, G9000165277, G9000221166, Dual-Mechanism Allosteric Inhibitors of ERK Signaling, Molecular basis for arrestin-mediated signaling
OpenAlex ID: W4289833967