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Sci. STKE, 15 March 2005
Vol. 2005, Issue 275, p. tw97
[DOI: 10.1126/stke.2752005tw97]


PATHWAY MAPPING Unraveling Signaling Networks

Understanding complex signaling networks is a difficult task that requires new and improved technology. Barrios-Rodiles et al. describe a method of tagging proteins that allows comprehensive mapping of interactions of suspected signaling proteins. High-throughput execution of more than 10,000 experiments yielded a signaling network activated by transforming growth factor-β (TGF-β), with more than 900 interactions. The dynamic nature of the network involved connections being both lost and gained as cells respond to TGF-β, which regulates the epithelial to mesenchymal transition that occurs during development and also contributes to invasive properties of carcinomas. Ozdamar et al. explored the regulation of tight junctions by TGF-β and the role of the polarity protein, Par6. Phosphorylation of Par6 by the TGF-β receptor was required for epithelial-to-mesenchymal transition of mammary gland cells. The function of Par6 appears to be recruitment of an E3 ubiquitin ligase (Smurf1), which leads to degradation of the small guanosine triphosphatase RhoA and dissolution of tight junctions.

M. Barrios-Rodiles, K. R. Brown, B. Ozdamar, R. Bose, Z. Liu, R. S. Donovan, F. Shinjo, Y. Liu, J. Dembowy, I. W. Taylor, V. Luga, N. Przulj, M. Robinson, H. Suzuki, Y. Hayashizaki, I. Jurisica, J. L. Wrana, High-throughput mapping of a dynamic signaling network in mammalian cells. Science 307, 1621-1625 (2005). [Abstract] [Full Text]

B. Ozdamar, R. Bose, M. Barrios-Rodiles, H.-R. Wang, Y. Zhang, J. L. Wrana, Regulation of the polarity protein Par6 by TGFß receptors controls epithelial cell plasticity. Science 307, 1603-1609 (2005). [Abstract] [Full Text]

Citation: Unraveling Signaling Networks. Sci. STKE 2005, tw97 (2005).

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