FIG 4.

Activation of ERK1/2 MAPK signaling by VopQ is dependent on IRE1 kinase activity. (A) Immunoblots for total Egr1, p-Erk1/2, and total Erk1/2 in starved wild-type (WT) MEFs that were untreated or treated with 4μ8c or KIRA6 inhibitors for 24 h and 1 h, respectively, and infected for 45 and 60 min with V. parahaemolyticus T3SS1⁺ or T3SS1⁻. Erk1/2 phosphorylation and increased Egr1 protein levels are not observed in MEFs treated with KIRA6 kinase inhibitor. Blots are representative of 3 independent experiments. (B) Model for IRE1-dependent modulation of Erk1/2 MAPK signaling by VopQ and VopS during V. parahaemolyticus infection. The green arrow indicates activation, and red lines depict inhibition. Dashed lines indicate postulated connections in the model requiring future study. Specifically, it is possible that Rho GTPases may be upstream of Ire1, and how VopQ’s inhibition of autophagic flux affects Ire1 signaling and vice versa is unclear.