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Sci. STKE, 23 November 2004
[DOI: 10.1126/stke.2602004tr8]

The Jak-STAT Pathway Stimulated by Interferon γ

Curt M. Horvath

1Department of Medicine, Evanston Northwestern Healthcare Research Institute, and Departments of Medicine and Biochemistry, Molecular Biology and Cell Biology, Northwestern University, Evanston, IL, 60208 USA.

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*Corresponding author. E-mail, curt.horvath{at}mssm.edu

Description

Different cytokines stimulate the Janus kinase (Jak) and signal transducer and activator of transcription (STAT) pathway. Interferon γ (IFN-γ) is a type II interferon that triggers antiviral responses through a Jak-STAT signaling pathway. These pathways involve a similar paradigm whereby cytokine binding to the receptor activates the Jaks, which phosphorylate STATs leading to their dimerization, translocation to the nucleus, and activation of their transcription factor activity. The animation shows binding of the ligand, dimerization of the receptors, activation of Jak1 and Jak2, and phosphorylation of STAT1 leading to dimerization, translocation to the nucleus, and stimulation of target gene expression. The consensus DNA sequence (the so-called GAS sequence) in the STAT1-responsive promoters is also depicted. Jak-STAT signaling is terminated by tyrosine phosphatases. Additional negative regulatory elements, such as PIAS1 and SOCS, are not shown in the animation.

This animation is useful in illustrating signaling through receptors that lack intrinsic catalytic activity through constitutive association of nonreceptor tyrosine kinases and the regulation of gene expression through phosphorylation-dependent dimerization and translocation of transcription factors in response to external stimuli. The animation illustrates the core, canonical signaling pathway activated in response to type II interferons, which are essential for mounting effective innate and adaptive immune responses.

The buttons at the top left allow the user to advance, rewind, or pause during the action. This animation was created by Carin Cain under the scientific oversight of Curt M. Horvath.

[Access Animation]

Educational Details

Learning Resource Type: Animation

Context: Undergraduate upper division, graduate, professional (degree program)

Intended Users: Teacher, learner

Intended Educational Use: Teach, learn

Discipline: Cell biology, molecular biology, immunology

Keywords: Signal transduction, transcription, gene expression, antiviral response, Jak, STAT

Technical Details

Format: Shockwave Flash Object (swf file)

Size: 47 kb

Requirements: Macromedia Flash (http://www.macromedia.com/downloads/)

Related Resources

Connections Map: D. Aaronson, C. M. Horvath, Interferon γ pathway. Sci. STKE (Connections Map, as seen November 2004), http://stke.sciencemag.org/cgi/cm/stkecm;CMP_9590. [Canonical Pathway]

Review: K. M. McBride, N. C. Reich, The ins and outs of STAT1 nuclear transport. Sci. STKE 2003, re13 (2003). [Gloss] [Abstract] [Full Text]

Virtual Journal: D. S. Aaronson, C. M. Horvath, A road map for those who don't know JAK-STAT. Science 296, 1653-1655 (2002). [Abstract] [Full Text]

Limits for Use

Cost: Free

Rights: This material may be downloaded, printed, linked to, and/or redistributed without modification for noncommercial, course teaching purposes only, provided credit to STKE is included by listing the citation for the teaching resource.

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Citation: C. M. Horvath, The Jak-STAT pathway stimulated by interferon γ. Sci. STKE 2004, tr8 (2004).

© 2004 American Association for the Advancement of Science


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