[en] SOCS3 (CIS3/JAB2) is an SH2-containing protein that binds to the activation loop of Janus kinases, inhibiting kinase activity, and thereby suppressing cytokine signaling. During embryonic development, SOCS3 is highly expressed in erythroid lineage cells and is Epo independent. Transgene-mediated expression blocks fetal erythropoiesis, resulting in embryonic lethality. SOCS3 deletion results in an embryonic lethality at 12-16 days associated with marked erythrocytosis. Moreover, the in vitro proliferative capacity of progenitors is greatly increased. SOCS3-deficient fetal liver stem cells can reconstitute hematopoiesis in lethally irradiated adults, indicating that its absence does not disturb bone marrow erythropoiesis. Reconstitution of lymphoid lineages in JAK3-deficient mice also occurs normally. The results demonstrate that SOCS3 is critical in negatively regulating fetal liver hematopoiesis.
Disciplines :
Biochemistry, biophysics & molecular biology
Author, co-author :
Marine, Jean-Christophe ; Université de Liège - ULiège > Département des sciences de la vie > GIGA-R : Biologie et génétique moléculaire ; Howard Hughes Medical Institute, and Department of Biochemistry, St. Jude Children's Research Hospital, Memphis, Tennessee 38105, USA
McKay, Catriona; Howard Hughes Medical Institute, St. Jude Children's Research Hospital, Memphis, TN 38105, United States ; Department of Biochemistry, St. Jude Children's Research Hospital, Memphis, TN 38105, United States
Wang, Demin; Department of Biochemistry, St. Jude Children's Research Hospital, Memphis, TN 38105, United States
Topham, David J.; Department of Immunology, St. Jude Children's Research Hospital, Memphis, TN 38105, United States
Parganas, Evan; Howard Hughes Medical Institute, St. Jude Children's Research Hospital, Memphis, TN 38105, United States ; Department of Biochemistry, St. Jude Children's Research Hospital, Memphis, TN 38105, United States
Nakajima, Hideaki; Department of Biochemistry, St. Jude Children's Research Hospital, Memphis, TN 38105, United States
Pendeville-Samain, Hélène ; Université de Liège - ULiège > Département des sciences de la vie > GIGA-R : Biologie et génétique moléculaire ; Department of Biochemistry, St. Jude Children's Research Hospital, Memphis, TN 38105, United States
Yasukawa, Hideo; Institute of Life Science, Kurume University, Kurume 839-0861, Japan
Sasaki, Atsuo; Institute of Life Science, Kurume University, Kurume 839-0861, Japan
Yoshimura, Akihiko; Institute of Life Science, Kurume University, Kurume 839-0861, Japan
Ihle, James N.; Howard Hughes Medical Institute, St. Jude Children's Research Hospital, Memphis, TN 38105, United States ; Department of Biochemistry, St. Jude Children's Research Hospital, Memphis, TN 38105, United States ; University of Tennessee, Medical School, Memphis, TN 38063, United States
Language :
English
Title :
SOCS3 is essential in the regulation of fetal liver erythropoiesis.
We would like to thank Irv Weismann (Stanford) for providing the pSP65-H2K-I-LTR vector for the transgenic studies. The authors would also like to thank Suzette Wingo for her excellent technical assistance. The ES cell line used in these studies was kindly provided by Jan van Deursen. This work is supported by the Cancer Center CORE grant CA21765, by the grant RO1 DK42932 to J. N. I., by grant PO1 HL53749, and by the American Lebanese Syrian Associated Charities (ALSAC).
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