John Libbey Eurotext



Functions of Jak kinases in hematopoiesis Volume 4, issue 5, Septembre-Octobre 1998


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Four tyrosine kinases of the Jak family are known in mammals : Jak1, Jak2, Jak3, and Tyk2. The function of these kinases was initially discovered through the study of interferon response. Biochemical data provided further evidence that the Jaks were activated by a large number of interleukins, hormones and growth factors and especially by cytokines that utilize receptors of the cytokine receptor superfamily. Recently, mice lacking Jak1, Jak2 and Tyk2 have been generated. The phenotype of these mice as well as the discovery of mutations on the two alleles of the human Jak3 gene in patients with autosomal severe combined immune deficiency confirmed the major role of the Jaks in cytokine-induced responses. The mutations cause a variety of defects that often include several hematopoietic lineages. This comes from the fact that only four Jaks participate to the signalling of nearly thirty cytokine receptors. Therefore, the lack of one Jak results in the lack of response to a set of cytokines. Alternatively, constitutive activation of Jak2 due to chromosomal rearrangement has been described in human leukemias. This review will focus on these recent data that enlight the major role of the Jak kinases in the control of hematopoietic cell proliferation.