Figure 8 | Cell Death & Disease

Figure 8

From: The synergistic interaction between the calcineurin B subunit and IFN-γ enhances macrophage antitumor activity

Figure 8

Diagram illustrating the mechanism of synergism between CnB and IFN-γ. CnB binds to an important macrophage membrane receptor integrin αM and activate p38 MAPK. Activated p38 promotes strong phosphorylation of STAT1 at Ser727 and weak phosphorylation at Tyr701. At the same time, IFN-γ binds to IFN-γ receptors (IFNGR) and strongly induces STAT1 Ser727 phosphorylation by p38 (or PKC-δ) and STAT1 Tyr701 phosphorylation by Jak2. Combination treatment with CnB and IFN-γ greatly enhances STAT1 serine and tyrosine phosphorylation and activates STAT1 maximally. The immense activation of STAT1 causes a sudden burst of TRAIL and other antitumor M1 cytokines directly or via the transcriptional factors IRF-1 and IRF-9 and finally render macrophages re-educated, possessing more ability to eradicate tumor. ‘+++’ represents strong activation and ‘+’ represents weak activation

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