The Jak-STAT Pathway Stimulated by Interleukin 6

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

Signal transducer and activator of transcription 3 (STAT3) is widely expressed and activated by a variety of growth-regulating signals, as well as diverse cytokines, that use gp130 signaling receptors. STAT3 is critical for embryonic development and stem cell biology, as well as inflammation, growth regulation, and multiple immune regulatory and homeostatic functions. The animation shows activation of STAT3 in response to interleukin 6 (IL6), a cytokine involved in triggering inflammation.

The animation shows binding of the ligand, dimerization of the receptors, activation of receptor-associated tyrosine kinases, Jak1 and Jak2, and phosphorylation of STAT1 leading to dimerization, translocation to the nucleus, and stimulation of target gene transcription. The consensus DNA sequence (the so-called SIE or GAS sequence) in the STAT3-responsive promoters is also depicted. Jak-STAT signaling is terminated by tyrosine phosphatases. Additional negative regulatory elements, such as PIAS3 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 pathway from Jak-associated receptors to phosphorylation and activation of STAT3. IL6 is implicated in chronic inflammatory disease and cancer, and this pathway is one potential therapeutic target for intervention.

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 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, inflammation, 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, STAT3 pathway. Sci. STKE (Connections Map, as seen November 2004), http://stke.sciencemag.org/cgi/cm/CMP_9229. [Canonical Pathway]

Perspective: Gerhard Müller-Newen, The cytokine receptor gp130: Faithfully promiscuous. Sci. STKE 2003, pe40 (2003).

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 interleukin 6. Sci. STKE 2004, tr9 (2004).

© 2004 American Association for the Advancement of Science