Open AccessA case of convergent evolution: Several viral and bacterial pathogens hijack RSK kinases through a common linear motif
Author(s) -
Frédéric Sorgeloos,
Michael Peeters,
Yohei Hayashi,
Fabian Borghese,
Nicolas Capelli,
Melissa Drappier,
Teresa Cesaro,
Didier Colau,
Vincent Stroobant,
Didier Vertommen,
Grégory de Bodt,
Stéphane Messe,
Ignasi Forné,
Felix Mueller-Planitz,
Jean-François Collet,
Thomas Michiels
Publication year - 2022
Publication title -
proceedings of the national academy of sciences of the united states of america
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.011
H-Index - 771
eISSN - 1091-6490
pISSN - 0027-8424
DOI - 10.1073/pnas.2114647119
Subject(s) - biology , kinase , protein kinase domain , microbiology and biotechnology , virology , genetics , gene , mutant
Significance Successful microbial infections typically involve the subversion of host immune pathways by pathogen-specific virulence factors. Here, we uncovered that viruses and bacteria independently evolved effectors targeting the same conserved loop of the mitogen-activated protein kinase (MAPK) p90-ribosomal S6-kinases (RSKs). Kinase usurpation relies on a previously unidentified short linear motif (SLiM) shared by these virulence factors. Mechanistically, RSK kinase binding prevents its dephosphorylation, thus promoting its phosphorylating activity. Remarkably, while viruses and bacteria evolved an identical mechanism of kinase activation, downstream effect diverged, effectively disarming different arms of the immune system according to their own need. This is a prominent illustration of trans-kingdom convergent evolution across microbial pathogens to usurp key signaling kinases.