Intracellular signal transduction of interferon on the suppression of haematopoietic progenitor cell growth
Authors: Kato K.; Kamezaki K.; Shimoda K.; Numata A.; Haro T.; Aoki K.; Ishikawa F.; Takase K.; Ariyama H.; Matsuda T.; Miyamoto T.; Nagafuji K.; Gondo H.; Nakayama K-I.; Harada M.
Source: British Journal of Haematology, Volume 123, Number 3, November 2003 , pp. 528-535(8)
Abstract:Summary. Interferon (IFN)- and IFN- suppress the growth of haematopoietic progenitor cells. IFN- activates Janus kinase-1 (Jak1) and Tyrosine kinase-2 (Tyk2), followed by the phosphorylation of the signal transducers and activators of transcription, Stat1 and Stat2. IFN- activates Jak1 and Jak2, followed by the activation of Stat1. Activated Stats bind the promoter regions of IFN-inducible genes. We evaluated the role of Tyk2 and Stat1 in the IFN-mediated inhibition of haematopoietic progenitor cell growth. While IFN- (1000 U/ml) suppressed the number of granulocyte-macrophage colony-forming units (CFU-GM) or erythroid burst-forming units (BFU-E) from wild-type mouse bone marrow cells, this suppression was partially inhibited by a deficiency in Tyk2 and completely inhibited by a deficiency in Stat1. High levels of IFN- (10 000 U/ml) suppressed the CFU-GM or BFU-E obtained from Stat1-deficient mice, but did not suppress this growth in cells from Tyk2-deficient mice. Stat1 was phosphorylated by IFN- in Tyk2-deficient cells, although the level of phosphorylation was weaker than that observed in wild type mice. Thus, the inhibitory signal on haematopoietic progenitor cells mediated by IFN- may be transduced by two signalling pathways, one regulated by Tyk2 and the other dependent on Stat1. IFN- also suppressed the number of CFU-GM or BFU-E, and this pathway was mediated by IFN- in a Stat1-dependent manner, independently of Tyk2.
Document Type: Research article
Publication date: 2003-11-01