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Interleukin-6-type cytokine signalling through the gp130/Jak/STAT pathway
P C Heinrich1, I Behrmann, G Müller-Newen
1Institut für Biochemie, RWTH Aachen, Universitätsklinikum, Pauwelsstrasse 30, D-52057 Aachen, Germany. Heinrich@RWTH-Aachen.de
The Biochemical Journal
|August 26, 1998
Summary
Interleukin-6 (IL-6)-type cytokines regulate cell processes via the gp130 receptor. This review details their signaling pathways, including Janus kinases (Jak) and signal transducers and activators of transcription (STAT) proteins, and termination mechanisms.
Area of Science:
- Cellular Biology
- Molecular Biology
- Immunology
Background:
- The interleukin-6 (IL-6)-type cytokine family, including IL-6 and others, signals through the common receptor subunit gp130.
- These cytokines are crucial for regulating gene activation, cell proliferation, and differentiation.
Purpose of the Study:
- To review the signal-transduction mechanisms of IL-6-type cytokines from the cell membrane to the nucleus.
- To discuss the roles of key signaling molecules and termination mechanisms.
Main Methods:
- Review of existing literature on IL-6-type cytokine signaling pathways.
- Focus on receptor complex assembly, Janus kinase (Jak) activation, and Signal Transducers and Activators of Transcription (STAT) family recruitment and phosphorylation.
Main Results:
- IL-6-type cytokines activate the gp130/Jak/STAT pathway, leading to gene transcription.
- Key players include cytokines, gp130 receptor components, Jak kinases (Jak1, Jak2, Tyk2), STATs (STAT1, STAT3), and SHP2 phosphatase.
- Signaling termination involves tyrosine phosphatases, proteasomes, SOCS, PIAS, and receptor internalization.
Conclusions:
- Despite sharing the gp130/Jak/STAT pathway, IL-6-type cytokines induce both similar and distinct biological responses.
- These distinct responses are evident in the varied phenotypes observed in cytokine knock-out animal models.