Jak2 is essential for signaling through a variety of cytokine receptors.
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, fail 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 gamma (IFNgamma), although the responses to IFNalpha/beta 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.
Parganas
E
E
Howard Hughes Medical Institute, Department of Biochemistry, St. Jude Children's Research Hospital, Memphis, Tennessee 38105, USA.
Wang
D
D
Stravopodis
D
D
Topham
D J
DJ
Marine
J C
JC
Teglund
S
S
Vanin
E F
EF
Bodner
S
S
Colamonici
O R
OR
van Deursen
J M
JM
Grosveld
G
G
Ihle
J N
JN
D000818:Animals; D001402:B-Lymphocytes / Q000166:cytology; D002454:Cell Differentiation; D003115:Colony-Stimulating Factors / Q000494:pharmacology; D016207:Cytokines / Q000494:pharmacology*; D004268:DNA-Binding Proteins / Q000235:genetics; D004920:Erythropoiesis / Q000235:genetics; D005347:Fibroblasts / Q000166:cytology; D006412:Hematopoietic Stem Cells / Q000166:cytology; D050856:Interferon Regulatory Factor-1; D053614:Janus Kinase 2; D008099:Liver / Q000166:cytology / Q000196:embryology; D051379:Mice; D018345:Mice, Knockout; D010641:Phenotype; D010750:Phosphoproteins / Q000235:genetics; D010766:Phosphorylation; D011505:Protein-Tyrosine Kinases / Q000235:genetics / Q000502:physiology*; D011518:Proto-Oncogene Proteins; D012333:RNA, Messenger / Q000032:analysis; D018121:Receptors, Cytokine / Q000502:physiology*; D015398:Signal Transduction / Q000502:physiology*; D013601:T-Lymphocytes / Q000166:cytology; D013926:Thrombopoietin / Q000494:pharmacology; D013950:Thymus Gland / Q000276:immunology; D014443:Tyrosine / Q000378:metabolism
D003115:Colony-Stimulating Factors; D016207:Cytokines; D004268:DNA-Binding Proteins; D050856:Interferon Regulatory Factor-1; C494258:Irf1 protein, mouse; D010750:Phosphoproteins; D011518:Proto-Oncogene Proteins; D012333:RNA, Messenger; D018121:Receptors, Cytokine; D014443:Tyrosine; D013926:Thrombopoietin; D011505:Protein-Tyrosine Kinases; C507926:Jak2 protein, mouse; D053614:Janus Kinase 2