The Jak-STAT Pathway Stimulated by Interferon α or Interferon β

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

Type I interferons, such as interferon α and interferon β (IFN-α and β), signal through a Janus kinase (Jak) to signal transduction and activator of transcription (STAT) pathway to stimulate gene expression. In response to ligand binding, the receptors dimerize, Jaks phosphorylate STAT1 and STAT2, which then dimerize along with a third transcriptional regulator IFN regulatory factor 9 (IRF9) to stimulate gene expression.

IFN-α is the main innate antiviral cytokine and is essential for effective immune response to viral infection.

The animation shows binding of the ligand, dimerization of the receptors, activation of Jak1 and Tyk2, and phosphorylation of STAT1 and STAT2, which dimerize and form a complex with IRF9. This complex, called ISGF3, translocates to the nucleus and stimulates expression of target genes. The consensus DNA sequence (the ISRE sequence) in the target promoters is also depicted. Jak-STAT signaling is terminated by tyrosine phosphatases.

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

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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, viral response, nonreceptor tyrosine kinase Jak, STAT

Technical Details

Format: Shockwave Flash Objects (swf file)

Size: 47 kb

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

Related Resources

Connections Map: D. Aaronson, C. M. Horvath, Type I interferon (alpha/beta IFN) pathway. Sci. STKE (Connections Map, as seen November 2004), http://stke.sciencemag.org/cgi/cm/stkecm;CMP_8390. [Canonical Pathway]

Review: R. M. Stroud, J. A. Wells, Mechanistic diversity of cytokine receptor signaling across cell membranes. Sci. STKE 2004, re7 (2004).

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 α or Interferon β. Sci. STKE 2004, tr10 (2004).

© 2004 American Association for the Advancement of Science