Cytokine‐inducible SH2 protein (CIS3) and JAK2 binding protein (JAB) abolish prolactin receptor‐mediated STAT5 signaling

FEBS Letters

Helman, Daniel²  Matsumoto, Akira³  Merchav, Shoshana¹  Gertler, Arieh²  Yoshimura, Akihiko³  Cohen, Yael²  Sandowski, Yael² 

[1] Haemopoiesis Unit, Department of Anatomy and Cell Biology, Rappaport Faculty of Medicine, Technion, Haifa 31096, Israel;Institute of Biochemistry, Food Science and Nutrition, Faculty of Agricultural, Food and Environmental Quality Sciences, The Hebrew University of Jerusalem, Rehovot 76100, Israel;Institute of Life Sciences, Kurume University, Aikiwamachi 2432-3, Kurume 839, Japan

关键词: Cytokine-inducible SH2 protein;    JAK2 binding protein;    Prolactin receptor;    Inhibition;    Cytokine signaling;   

DOI  :  10.1016/S0014-5793(98)01555-5

学科分类：生物化学/生物物理

来源: John Wiley & Sons Ltd.

【 摘 要 】

The ability of five members of the cytokine-inducible SH2 protein family (CIS1–4) and JAK2 binding (JAB) protein to affect prolactin receptor (PRLR)-mediated activity was tested in human 293 embryonic kidney fibroblasts transiently transfected with rat PRLR, five concentrations of CIS/JAB Myc-tagged cDNAs and a STAT5-responsive reporter gene encoding luciferase. The protein expressions of CIS1, CIS2, CIS3 and JAB were comparable, whereas the level of CIS4 was slightly lower. PRLR-mediated luciferase activity was abolished in a dose-dependent manner in cells transfected with cDNA of CIS3 or JAB, even at concentrations below the level of protein detection by anti-Myc antibody. In contrast, CIS1, CIS2 and CIS4 had little or no effect, despite similar levels of expression. CIS1 expression in postpartum mouse mammary glands was high and changed little in the course of 3 days. CIS2 and CIS3 expression was also high and increased further, whereas JAB expression was very low. These results hint that at least in mammary gland CIS3 is likely the main physiological negative regulator of the PRLR-mediated JAK2/STAT5 pathway.

【 授权许可】

Unknown