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Fig. 9 Schematic of the human GH-induced activation of STAT5b. Human STAT5b protein variants p.Ala630Pro, p.Gln474Arg and p.Lys632Asn are shown in bold and the potential mechanisms of interference in the endogenous stat5.1 intracellular signaling cascade are shown in boxes. All variants, including WT, p.Ala630Pro, p.Gln474Arg and p.Lys632Asn STAT5b can interfere with endogenous stat5.1 through the formation of less functional STAT5b/stat5.1 hetero-dimers. In addition, variant p.Ala630Pro can interfere with endogenous stat5.1 by aggregation and through the formation of cytoplasmic inclusions. Variant p.Gln4747Arg can interfere by reduced DNA-binding affinity of the STAT5b/stat5.1 hetero-dimers. Finally, variant p.Lys632Asn can interfere by its increased affinity of SH2 docking to activated GHR.