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. 2018 Jun 22;19(7):1843. doi: 10.3390/ijms19071843

Figure 2.

Figure 2

The SOCS proteins mechanisms of GHR-JAK2-STAT pathway inhibition. The SOCS1, 2, 3 and CIS have the same mechanism of phosphorylation inhibition of STAT by competitive binding to phosphotyrosines of the GHR. The SOCS1 and SOCS3, because of the KIR domain presence, can act also in a different manner. Both of them can bind to JAK2; however, SOCS1 can bind directly to JAK2 inhibiting its enzymatic activity and SOCS3 before binding to JAK2 requires binding to GHR, which leads to degradation of the GHR-JAK2 complex directly or indirectly by ubiquitination. Another mechanism of SOCS1 and SOCS3 action is dependent on the PIM-1 protein, which probably stabilizes their phosphorylation and prolongs their inhibitory action. CIS, SOCS—suppressors of cytokine signaling; Box 1—proline-rich domain; GHR—growth hormone receptor; JAK2—Janus kinase 2; FERM—N-terminal 4.1, Ezrin, Radixin, Moesin domain; KIR—kinase inhibitory region; P—phosphorylation marker; PIM-1—proto-oncogene serine/threonine-protein kinase; STAT—signal transducer and activator of transcription; Ub—ubiquitination.