TY - JOUR
T1 - Cytokine-inducible SH2 protein (CIS3) and JAK2 binding protein (JAB) abolish prolactin receptor-mediated STAT5 signaling
AU - Helman, Daniel
AU - Sandowski, Yael
AU - Cohen, Yael
AU - Matsumoto, Akira
AU - Yoshimura, Akihiko
AU - Merchav, Shoshana
AU - Gertler, Arieh
N1 - Funding Information:
The authors acknowledge Prof. P.A. Kelly and Dr. V. Goffin from INSERM U366 (Paris, France) for providing us with the 293 cells and the vectors encoding luciferase and rPRLR. We also thank Dr. R. Hooghe, Prof. E. Hooghe-Peters and Dr. B. Velkeniers from the Free University of Brussels (Belgium) for encouraging us to enter this field and for reviewing the manuscript. This work (μg A.G. and S.M.) was partially supported by a grant (to B. Velkeniers) from the Ministry of Scientific Research of the Brussels-Capital Region.
PY - 1998/12/18
Y1 - 1998/12/18
N2 - 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.
AB - 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.
KW - Cytokine signaling
KW - Cytokine-inducible SH2 protein
KW - Inhibition
KW - JAK2 binding protein
KW - Prolactin receptor
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U2 - 10.1016/S0014-5793(98)01555-5
DO - 10.1016/S0014-5793(98)01555-5
M3 - Article
C2 - 9883901
AN - SCOPUS:0032418093
SN - 0014-5793
VL - 441
SP - 287
EP - 291
JO - FEBS Letters
JF - FEBS Letters
IS - 2
ER -