A case of convergent evolution: Several viral and bacterial pathogens hijack RSK kinases through a common linear motif

• DOI: 10.1073/pnas.2114647119
• Publication Date: 2022-01-28T21:10:56Z
• Authors: 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-Pla...; Jean-François Collet; Thomas Michiels
• Keywords: Gene Expression Regulation, Viral; MAP Kinase Signaling System; Virus Replication; Ribosomal Protein S6 Kinases, 90-kDa; Cell Line; Immediate-Early Proteins; 03 medical and health sciences; Humans; innate immunity; [SDV.IMM.II] Life Sciences [q-bio]/Immunology/Innate immunity; type-3 secretion; Mitogen-Activated Protein Kinase Kinases; 0303 health sciences; Bacteria; Host Microbial Interactions; Bacterial Infections; Biological Sciences; Biological Evolution; short linear motif; 3. Good health; picornavirus; Virus Diseases; Viruses; [SDV.MHEP.MI] Life Sciences [q-bio]/Human health and pathology/Infectious diseases; host–pathogen interaction

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.