Structure and function of a new STAT-induced STAT inhibitor

Tetsuji Naka, Masashi Narazaki, Moritoshi Hirata, Tomoshige Matsumoto, Seijiro Minamoto, Atsufumi Aono, Norihiro Nishimoto, Tadahiro Kajita, Tetsuya Taga, Kazuyuki Yoshizaki, Shizuo Akira and Tadamitsu Kishimoto ()
Additional contact information
Tetsuji Naka: Yamada-Oka
Masashi Narazaki: Yamada-Oka
Moritoshi Hirata: Yamada-Oka
Tomoshige Matsumoto: Yamada-Oka
Seijiro Minamoto: Yamada-Oka
Atsufumi Aono: Yamada-Oka
Norihiro Nishimoto: Medical Science I, School of Health and Sports Sciences, Yamada-Oka
Tadahiro Kajita: ‡Research and Development Center, International Reagents Corporation, 1-2, 1-Chome, Murotani
Tetsuya Taga: Medical Research Institute, Tokyo Medical and Dental University. 2-3-10, Kanda-Surugadai
Kazuyuki Yoshizaki: Medical Science I, School of Health and Sports Sciences, Yamada-Oka
Shizuo Akira: 1-1, Mukogawa
Tadamitsu Kishimoto: Yamada-Oka

Nature, 1997, vol. 387, issue 6636, 924-929

Abstract: Abstract The signalling pathway that comprises JAK kinases and STAT proteins (for signal transducer and activator of transcription) is important for relaying signals from various cytokines outside the cell to the inside1,2,3. The feedback mechanism responsible for switching off the cytokine signal has not been elucidated. We now report the cloning and characterization of an inhibitor of STAT activation which we name SSI-1 (for STAT-induced STAT inhibitor-1). We found that SSI-1 messenger RNA was induced by the cytokines interleukins 4 and 6 (IL-4, IL-6), leukaemia-inhibitory factor (LIF), and granulocyte colony-stimulating factor (G-CSF). Stimulation by IL-6 or LIF of murine myeloid leukaemia cells (M1 cells) induced SSI-1 mRNA expression which was blocked by transfection of a dominant-negative mutant of Stat3, indicating that the SSI-1 gene is a target of Stat3 (refs 4, 5, 6, 7). Forced overexpression of SSI-1 complementary DNA interfered with IL-6- and LIF-mediated apoptosis and macrophage differentiation of M1 cells, as well as IL-6 induced tyrosine-phosphorylation of a receptor glycoprotein component, gp130, and of Stat3. When SSI-1 is overexpressed in COS7 cells, it can associate with the kinases Jak2 and Tyk2. These findings indicate that SSI-1 is responsible for negative-feedback regulation of the JAK–STAT pathway induced by cytokine stimulation.

Date: 1997
References: Add references at CitEc
Citations: View citations in EconPapers (1)

Downloads: (external link)
https://www.nature.com/articles/43219 Abstract (text/html)
Access to the full text of the articles in this series is restricted.

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:nature:v:387:y:1997:i:6636:d:10.1038_43219

Ordering information: This journal article can be ordered from
https://www.nature.com/

DOI: 10.1038/43219

Access Statistics for this article

Nature is currently edited by Magdalena Skipper

More articles in Nature from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().