TY - JOUR
T1 - Jak2 is essential for signaling through a variety of cytokine receptors
AU - Parganas, Evan
AU - Wang, Demin
AU - Stravopodis, Dimitrios
AU - Topham, David J.
AU - Marine, Jean Christophe
AU - Teglund, Stephan
AU - Vanin, Elio F.
AU - Bodner, Sara
AU - Colamonici, Oscar R.
AU - Van Deursen, Jan M.
AU - Grosveld, Gerard
AU - Ihle, James N.
N1 - Funding Information:
We would like to thank Linda Snyder for her excellent technical assistance in conducting the studies and John F. Zacher for his excellent photography skills. This work was supported in part by Cancer Center CORE Grant CA21765, by grant RO1 DK42932 to J. N. I., and by the American Lebanese Syrian Associated Charities.
PY - 1998/5/1
Y1 - 1998/5/1
N2 - A variety of cytokines activate receptor-associated members of the Janus family of protein tyrosine kinases (Jaks). To assess the role of Jak2, we have derived Jak2-deficient mice. The mutation causes an embryonic lethality due to the absence of definitive erythropoiesis. Fetal liver myeloid progenitors, although present based on the expression of lineage specific markers, fall to respond to erythropoietin, thrombopoietin, interleukin-3 (IL-3), or granulocyte/macrophage colony-stimulating factor. In contrast, the response to granulocyte specific colony-stimulating factor is unaffected. Jak2-deficient fibroblasts failed to respond to interferon γ (IFNγ), although the responses to IFNα/β and IL-6 were unaffected. Lastly, reconstitution experiments demonstrate that Jak2 is not required for the generation of lymphoid progenitors, their amplification, or functional differentiation. Therefore, Jak2 plays a critical, nonredundant role in the function of a specific group of cytokines receptors.
AB - A variety of cytokines activate receptor-associated members of the Janus family of protein tyrosine kinases (Jaks). To assess the role of Jak2, we have derived Jak2-deficient mice. The mutation causes an embryonic lethality due to the absence of definitive erythropoiesis. Fetal liver myeloid progenitors, although present based on the expression of lineage specific markers, fall to respond to erythropoietin, thrombopoietin, interleukin-3 (IL-3), or granulocyte/macrophage colony-stimulating factor. In contrast, the response to granulocyte specific colony-stimulating factor is unaffected. Jak2-deficient fibroblasts failed to respond to interferon γ (IFNγ), although the responses to IFNα/β and IL-6 were unaffected. Lastly, reconstitution experiments demonstrate that Jak2 is not required for the generation of lymphoid progenitors, their amplification, or functional differentiation. Therefore, Jak2 plays a critical, nonredundant role in the function of a specific group of cytokines receptors.
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U2 - 10.1016/S0092-8674(00)81167-8
DO - 10.1016/S0092-8674(00)81167-8
M3 - Article
C2 - 9590173
AN - SCOPUS:0032076542
SN - 0092-8674
VL - 93
SP - 385
EP - 395
JO - Cell
JF - Cell
IS - 3
ER -