Signalling in multicellular organisms is mediated by complex networks that integrate extracellular and intracellular signals to generate appropriate responses regulating cell proliferation, differentiation and survival. Downstream of many cytokine and growth hormone receptors, receptor-associated JAKs (Janus kinases) activate transcription factors of the STAT (signal transducer and activator of transcription) protein family and thereby mediate signal transduction from the plasma membrane to the nucleus. The JAK/STAT pathway has been shown to be constitutively activated in a wide array of human malignancies. To elucidate mechanisms contributing to tumour formation and identify system properties of the JAK/STAT signalling pathway, a systems biology approach can be employed. So far the majority of studies available have focused on down-regulation of the signalling pathway based on simulations. However, a data-based model of the core module of the JAK2/STAT5 signalling pathway showed that rapid nucleocytoplasmic cycling of STAT5 is an essential pathway property. In the future, combining assays for quantitative analysis at different levels will be important to gain deeper insight into molecular mechanisms regulating intracellular communication mediated by such complex dynamic systems as signalling pathways and their targets.
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September 2008
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Review Article|
September 30 2008
Systems biology of JAK/STAT signalling
Andrea C. Pfeifer;
Andrea C. Pfeifer
*Division Systems Biology of Signal Transduction, German Cancer Research Center, Im Neuenheimer Feld 280, 69120 Heidelberg, Germany
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Jens Timmer;
Jens Timmer
†Freiburg Center for Data Analysis and Modelling, University of Freiburg, Eckertstrasse 1, 79104 Freiburg, Germany
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Ursula Klingmüller
Ursula Klingmüller
1
*Division Systems Biology of Signal Transduction, German Cancer Research Center, Im Neuenheimer Feld 280, 69120 Heidelberg, Germany
1To whom correspondence should be addressed (email u.klingmueller@dkfz-heidelberg.de).
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Publisher: Portland Press Ltd
Online ISSN: 1744-1358
Print ISSN: 0071-1365
© The Authors Journal compilation © 2008 Biochemical Society
2008
Essays Biochem (2008) 45: 109–120.
Citation
Olaf Wolkenhauer, Peter Wellstead, Kwang-Hyun Cho, Andrea C. Pfeifer, Jens Timmer, Ursula Klingmüller; Systems biology of JAK/STAT signalling. Essays Biochem 30 September 2008; 45 109–120. doi: https://doi.org/10.1042/bse0450109
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