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

• Published in: FEBS letters 1998-12, Vol.441 (2), p.287-291
• Main Authors: Helman, Daniel, Sandowski, Yael, Cohen, Yael, Matsumoto, Akira, Yoshimura, Akihiko, Merchav, Shoshana, Gertler, Arieh
• Format: Article
• Language: English
• Subjects: Animals; Carrier Proteins - metabolism; Cattle; Cell Line; Cytokine signaling; Cytokine-inducible SH2 protein; DNA-Binding Proteins - metabolism; Female; Humans; Inhibition; Intracellular Signaling Peptides and Proteins; JAK2 binding protein; Mammary Glands, Animal - metabolism; Mice; Milk Proteins; Placental Lactogen - biosynthesis; Postpartum Period; Prolactin receptor; Proteins - metabolism; Rats; Receptors, Prolactin - metabolism; Recombinant Proteins - biosynthesis; Repressor Proteins; Signal Transduction; src Homology Domains; STAT5 Transcription Factor; Suppressor of Cytokine Signaling 1 Protein; Suppressor of Cytokine Signaling 3 Protein; Suppressor of Cytokine Signaling Proteins; Trans-Activators - metabolism; Transcription Factors
• ISSN: 0014-5793; 1873-3468
• DOI: 10.1016/S0014-5793(98)01555-5

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.