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Model for regulation of ASK1 by JAK2 kinase and SHP2 phosphatase. In resting or IFN-γ-treated EC, JAK2 phosphorylates ASK1 at Tyr(P)-718, which enhances the interaction between SOCS1 and ASK1, leading to ASK1 proteasomal degradation. In contrast, SHP2, an SH2 domain-containing tyrosine phosphatase that can be activated by TNF, dephosphorylates ASK1 at Tyr-718 and dissociates ASK1 from SOCS1, stabilizing ASK1 and activating ASK1-JNK apoptotic pathway in EC. Ub, ubiquitin.
