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. 2020 Sep 25;11:558341. doi: 10.3389/fimmu.2020.558341

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Copyright © 2020 Huang, Liu, Cheng, Wang, Cui, Huang, Zhu, Chen, Liu, Zhao, Wu, Yang, Zhang, Ou, Mao, Gao, Yu, Tian, Liu, Zhang, Yin, Jing, Chen and Jia.

This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

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The production and action of SOCS proteins. Various cytokine receptors can induce SOCS proteins expression in a JAK/STAT-dependent manner (Pictured on the left side). However, SOCS1, SOCS3 and CIS seem to suppress signaling in various ways. SOCS1 directly interacts with JAKs and reduce their catalytic activities while SOCS3 interacts with the proximal position and CIS blocks up with the binding sites of STATs to receptors. Moreover, it is possible to induce the production of SOCS proteins independent of JAK/STAT signaling pathways, such as signaling of TLRs, growth factor receptors (GFRs). (a) The SOCS proteins induced in these ways could inhibit the response of the cell to other cytokines, which is one of the modes of crosstalk inhibition. Finally, the inhibition of SOCS proteins may not be limited to the classic JAK/STAT signaling pathway (b,c). The figure is referenced from Figure 1 of Suppressors of cytokine signaling and immunity (14). The red line indicates inhibition; green line indicates promotion; P (in the green circle) indicates phosphorylated.