Jak2 is essential for signaling through a variety of cytokine receptors

Evan Parganas, Demin Wang, Dimitrios Stravopodis, David J. Topham, Jean Christophe Marine, Stephan Teglund, Elio F. Vanin, Sara Bodner, Oscar R. Colamonici, Jan M. Van Deursen, Gerard Grosveld, James N. Ihle

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834 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)385-395
Number of pages11
JournalCell
Volume93
Issue number3
DOIs
StatePublished - May 1 1998

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

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    Parganas, E., Wang, D., Stravopodis, D., Topham, D. J., Marine, J. C., Teglund, S., Vanin, E. F., Bodner, S., Colamonici, O. R., Van Deursen, J. M., Grosveld, G., & Ihle, J. N. (1998). Jak2 is essential for signaling through a variety of cytokine receptors. Cell, 93(3), 385-395. https://doi.org/10.1016/S0092-8674(00)81167-8