DDVF-mediated modulation of ERK signaling in TMEV-infected cells.

<p><b>A.</b> Immunoblot analysis of L929 cells infected with TMEV derivatives expressing either the wild-type L protein (L-DDVF) or its mutants (L-DDVA and L-M60V) compared to uninfected controls (n = 4). Phospho-ERK (pERK) and total ERK levels were assessed. Viral 3D polymerase de...

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Main Author: Martin Veinstein (20958024) (author)
Other Authors: Vincent Stroobant (2073988) (author), Fanny Wavreil (14248238) (author), Thomas Michiels (76922) (author), Frédéric Sorgeloos (427428) (author)
Published: 2025
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Summary:<p><b>A.</b> Immunoblot analysis of L929 cells infected with TMEV derivatives expressing either the wild-type L protein (L-DDVF) or its mutants (L-DDVA and L-M60V) compared to uninfected controls (n = 4). Phospho-ERK (pERK) and total ERK levels were assessed. Viral 3D polymerase detection served as an infection control. <b>B.</b> Quantification of the pERK/ERK ratio from the immunoblots shown in panel A (n = 4). <b>C.</b> Proposed model of RSK-mediated ERK-MAPK regulation by L during TMEV infection. The DDVF motif of L competes with host ERK-MAPK proteins containing DDVF motifs, thereby inhibiting DDVF-mediated negative feedback on the ERK-MAPK pathway. In the absence of a functional DDVF motif in <b>L</b> (mutant forms, shown in green), the virus does not dysregulate the MAPK pathway. Proteins in the MAPK pathway with DDVF motifs (e.g., SPRED2, GAB3, CNKSR2, FGFR1, SOS1, etc.) are shown in purple. Activated RSK and ERK kinases are represented by red shading.</p>