| Autor: |
Sakamoto, Hiroshi, Yasukawa, Hideo, Masuhara, Masaaki, Tanimura, Shyu, Sasaki, Atsuo, Yuge, Kentaro, Ohtsubo, Motoaki, Ohtsuka, Akira, Fujita, Takasi, Ohta, Tsunetaka, Furukawa, Yusuke, Iwase, Satsuki, Yamada, Hisashi, Yoshimura, Akihiko |
| Zdroj: |
Blood; September 1998, Vol. 92 Issue: 5 p1668-1676, 9p |
| Abstrakt: |
It has been shown that interferons (IFNs) exert their signals through receptor-associated Janus kinases (JAKs) and signal transducers and activators of transcription (STATs). However, molecular mechanism of regulation of IFN signaling has not been fully understood. We have reported novel cytokine-inducible SH2 protein (CIS) and JAK binding protein (JAB) family genes that can potentially modulate cytokine signaling. Here we report that JAB is strongly induced by IFN-? but not by IFN-ß in mouse myeloid leukemia M1 cells and NIH-3T3 fibroblasts. NIH-3T3 cells ectopically expressing JAB but not CIS3 lost responsiveness to the antiviral effect of IFN-ß and IFN-?. M1 leukemic cells stably expressing JAB were also resistant to IFN-? and IFN-ß–induced growth arrest. In both NIH-3T3 and M1 transformants expressing JAB, IFN-? did not induce tyrosine phosphorylation and DNA binding activity of STAT1. Moreover, IFN-?–induced activation of JAK1 and JAK2 and IFN-ß–induced JAK1 and Tyk2 activation were inhibited in NIH-3T3 JAB transformants. These results suggest that JAB inhibits IFN signaling by blocking JAK activity. We also found that IFN-resistant clones derived from LoVo cells and Daudi cells expressed high levels of JAB without stimulation. In IFN-resistant Daudi cells, IFN-induced STAT1 and JAK phosphorylation was partially reduced. Therefore, overexpression of JAB could be, at least in part, a mechanism of IFN resistance. © 1998 by The American Society of Hematology. |
| Databáze: |
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