Note to users. If you're seeing this message, it means that your browser cannot find this page's style/presentation instructions -- or possibly that you are using a browser that does not support current Web standards. Find out more about why this message is appearing, and what you can do to make your experience of our site the best it can be.

Site Tools

  • AAAS
  • Subscribe
  • Feedback

Site Search

Search Advanced

Science 17 October 2008:
Vol. 322. no. 5900, pp. 453 - 456
DOI: 10.1126/science.1158739
Prev | Table of Contents | Next

Reports

Phosphorylation Networks Regulating JNK Activity in Diverse Genetic Backgrounds

Chris Bakal,1,2*{dagger} Rune Linding,3* Flora Llense,4* Elleard Heffern,2 Enrique Martin-Blanco,4 Tony Pawson,5 Norbert Perrimon1,2

Cellular signaling networks have evolved to enable swift and accurate responses, even in the face of genetic or environmental perturbation. Thus, genetic screens may not identify all the genes that regulate different biological processes. Moreover, although classical screening approaches have succeeded in providing parts lists of the essential components of signaling networks, they typically do not provide much insight into the hierarchical and functional relations that exist among these components. We describe a high-throughput screen in which we used RNA interference to systematically inhibit two genes simultaneously in 17,724 combinations to identify regulators of Drosophila JUN NH2-terminal kinase (JNK). Using both genetic and phosphoproteomics data, we then implemented an integrative network algorithm to construct a JNK phosphorylation network, which provides structural and mechanistic insights into the systems architecture of JNK signaling.

1 Department of Genetics, Harvard Medical School, 77 Avenue Louis Pasteur, Boston, MA 02215, USA.
2 Howard Hughes Medical Institute, Harvard Medical School, Boston, MA 02215, USA.
3 Cellular & Molecular Logic Team, The Institute for Cancer Research, 237 Fulham Road, London SW3 6JB, UK.
4 Institut de Biologia Molecular de Barcelona, CSIC (Spanish Council for Scientific Research), Parc Científic de Barcelona, 08028 Spain.
5 Samuel Lunenfeld Research Institute, Mount Sinai Hospital, 600 University Avenue, Toronto, Ontario M5G 1X5, Canada.

* These authors contributed equally to this work

{dagger} To whom correspondence should be addressed. E-mail: cbakal{at}receptor.med.harvard.edu

Read the Full Text


THIS ARTICLE HAS BEEN CITED BY OTHER ARTICLES:
Science Signaling Podcast: 28 October 2008.
R. Linding and A. M. VanHook (2008)
Science Signaling 1, pc10
   Abstract »    Full Text »


To Advertise     Find Products

Science. ISSN 0036-8075 (print), 1095-9203 (online)