CIS1 interacts with the Y532 of the prolactin receptor and suppresses prolactin-dependent STAT5 activation.

摘要: Prolactin (PRL) interacts with a single-chain prolactin-specific receptor of the cytokine superfamily. PRL triggers activation JAK2 kinase, which phosphorylates itself, and STAT5, member family signal transducers activators transcription (STAT). We have shown that STAT5-dependent immediate early gene, CIS1 (Cytokine-Inducible SH2 domain-containing protein-1), suppresses PRL-induced STAT5 in vitro as well transgenic mice. To facilitate study interactions between receptor, we developed yeast tri-hybrid system, modification two-hybrid system. expressed fused to DNA-binding domain cytoplasmic presence or absence tyrosine kinase yeast. bound JAK2-dependent manner. Moreover, determined phosphorylated Y532 murine is binding site for CIS1. Interestingly, has been be unnecessary activation, although overexpression suppressed activation. These data suggest suppression by not due simple competition but rather binding.