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

Daniel Helman, Yael Sandowski, Yael Cohen, Akira Matsumoto, Akihiko Yoshimura, Shoshana Merchav, Arieh Gertler

Research output: Contribution to journalArticle

65 Citations (Scopus)

Abstract

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. Copyright (C) 1998 Federation of European Biochemical Societies.

Original languageEnglish
Pages (from-to)287-291
Number of pages5
JournalFEBS Letters
Volume441
Issue number2
DOIs
Publication statusPublished - 1998 Dec 18
Externally publishedYes

Keywords

  • Cytokine signaling
  • Cytokine-inducible SH2 protein
  • Inhibition
  • JAK2 binding protein
  • Prolactin receptor

ASJC Scopus subject areas

  • Biophysics
  • Structural Biology
  • Biochemistry
  • Molecular Biology
  • Genetics
  • Cell Biology

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