Scheme 2.

Schematic diagram of the hypothesized model of ubiquitination at the level of Uba1: Entry of SAK-HV into the RAW264.7 cells could partially inhibit the ubiquitination function of Uba1 through the interaction of its SAK-mutant functional domain and Uba1. This inhibition reduces the level of self-ubiquitination of MEKK1 by reducing the interaction between Uba1 and particular E2 enzymes to increase its kinase activity, which activates the MAPK/ERK and JNK pathways through downstream phosphorylation. Finally, macrophage proliferation is induced at the output of these cascades. The gray dotted line represents the blocked regulation between upstream and down stream. The gray pathway names indicates that these pathways are inactivated. Abbreviation: Ub, ubiquitin; pERK, phosphorylation of ERK pathway; pJNK, phosphorylation of JNK pathway.