Schematic of the human GH-induced activation of STAT5B. (A) Schematic of the human STAT5B peptide (upper schematic) and encoding exons (lower schematic). The domains indicated: ND, N-terminal domain; CCD, coil-coiled domain; DBD, DNA binding domain; L, linker domain; SH2, Src-homology 2 domain; TAD, transactivation domain. Tyrosine 699 (Y699) that can be phosphorylated by JAK2 and other kinases. (B) Recruitment and activation of STAT5B to the human growth hormone receptor (GHR): (i) Upon GH-GHR interactions, STAT5B docks to 3 of the 7 JAK2-phosphorylated tyrosines (Y) on activated intracellular domain of GHR; (ii) the recruited STAT5B is Tyr699 (Y699) phosphorylated by JAK2; (iii) Phosphorylated STAT5B homo-dimerize, translocate to the nucleus where it binds DNA and transcriptionally regulated genes such as IGF1, IGFBP3 and IGFALS. Broken arrows, translocation process.