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

Figure 5.

Figure 5

GHR-JAK2-STAT pathway inhibition mediated by PTP-1B, SHP-1, SHP2 and SIRPα1. PTP-1B dephosphorylates residual tyrosines of JAK2, GHR, STAT3 or STAT5. PTP-H1 dephosphorylates GHR acting through the JAK2 activity down-regulation. SHP-1 mechanism of action: direct dephosphorylation of JAK2; targeting of the SOCS1–Grb2 complex to JAK2; dephosphorylation of STAT5β in nucleus. SHP-2 mechanism of action: direct dephosphorylation of STAT, binding of SHP-2 to phosphotyrosines and dephosphorylation of GHR complex; binding of SHP-2 to JAK2 via SIRPα1. SIRPα1 after the GHR activation binds to JAK2 and creates binding site for SHP-2. Box 1—proline-rich domain; FERM—N-terminal 4.1, Ezrin, Radixin, Moesin domain; GHR—growth hormone receptor; Grb2—growth factor receptor-bound protein 2; JAK2—Janus kinase 2; P—phosphorylation marker; PTP—Protein tyrosine phosphatase; SHP—Src homology phosphatase; SOCS1—suppressor of cytokine signaling 1; STAT—signal transducer and activator of transcription.