G4600x Signal Transduction Fall 2007

Tuesdays 4:10 - 6:00 P.M. 800 Fairchild

Professors Ron Prywes (first half) and Daniel Kalderon (second half).

Prerequisites: Enrollment in the graduate program in Biological Sciences or permission of the instructor. Generally students with a solid background in biology (four or more courses) are accepted.

Text: The Biochemistry of Signal Transduction and Regulation, Third edition by Gerhard Krauss. This book has been ordered in the bookstore.

Course Requirements:

Students are required to read all research papers for discussion. They will also present specific papers to the class. There will be a midterm exam on October 16. In the second half of the course there will be problem set homework and a final paper is due on the last day of class. The final paper will consist of a research proposal with specific aims, background and research design sections. It should be 10-15 double-spaced pages. The topic must be approved by an instructor.

1. September 4 Growth Factors and Receptors

1. Ferguson, K.M., Berger, M.B., Mendrola, J.M., Cho, H.S., Leahy, D.J. and Lemmon, M.A. (2003) EGF activates its receptor by removing interactions that autoinhibit ectodomain dimerization. Mol Cell 11(2), 507-17.

2. Yuzawa, S., Opatowsky, Y., Zhang, Z., Mandiyan, V., Lax, I. and Schlessinger, J. (2007) Structural Basis for Activation of the Receptor Tyrosine Kinase KIT by Stem Cell Factor. Cell 130(2), 323-34.

Text: Chapter 3, p. 115-142, Chapter 8, p. 311-323 and Chapters 11 and 12.

2. September 11 Adapters

3. Hardy, W.R., Li, L., Wang, Z., Sedy, J., Fawcett, J., Frank, E., Kucera, J. and Pawson, T. (2007) Combinatorial ShcA docking interactions support diversity in tissue morphogenesis. Science 317(5835), 251-6.

4. Machida, K., Thompson, C.M., Dierck, K., Jablonowski, K., Karkkainen, S., Liu, B., Zhang, H., Nash, P.D., Newman, D.K., Nollau, P., Pawson, T., Renkema, G.H., Saksela, K., Schiller, M.R., Shin, D.G. and Mayer, B.J. (2007) High-throughput phosphotyrosine profiling using SH2 domains. Mol Cell 26(6), 899-915.

Text: p. 328-336, 351-353.

3. September 18 MAP Kinases

5. Douziech, M., Sahmi, M., Laberge, G. and Therrien, M. (2006) A KSR/CNK complex mediated by HYP, a novel SAM domain-containing protein, regulates RAS-dependent RAF activation in Drosophila. Genes Dev 20(7), 807-19.

6. von Kriegsheim, A., Pitt, A., Grindlay, G.J., Kolch, W. and Dhillon, A.S. (2006) Regulation of the Raf-MEK-ERK pathway by protein phosphatase 5. Nat Cell Biol 8(9), 1011-6.

Text: Chapter 10

4. September 25 G protein, ras and rho family signaling

7. Jura, N., Scotto-Lavino, E., Sobczyk, A. and Bar-Sagi, D. (2006) Differential modification of Ras proteins by ubiquitination. Mol Cell 21(5), 679-87.

8. Zhao, C., Du, G., Skowronek, K., Frohman, M.A. and Bar-Sagi, D. (2007) Phospholipase D2-generated phosphatidic acid couples EGFR stimulation to Ras activation by Sos. Nat Cell Biol 9(6), 706-12.

Text: Chapters 5 and 9

5. October 2 Phosphatidylinositol

9. Sarbassov, D.D., Guertin, D.A., Ali, S.M. and Sabatini, D.M. (2005) Phosphorylation and regulation of Akt/PKB by the rictor-mTOR complex. Science 307(5712), 1098-101.

10. Guertin, D.A., Stevens, D.M., Thoreen, C.C., Burds, A.A., Kalaany, N.Y., Moffat, J., Brown, M., Fitzgerald, K.J. and Sabatini, D.M. (2006) Ablation in mice of the mTORC components raptor, rictor, or mLST8 reveals that mTORC2 is required for signaling to Akt-FOXO and PKCalpha, but not S6K1. Dev Cell 11(6), 859-71.

Text: p. 237-241, 248-253, 259-260

6. October 9 Nuclear signalling

11. Cam, H., Balciunaite, E., Blais, A., Spektor, A., Scarpulla, R.C., Young, R., Kluger, Y. and Dynlacht, B.D. (2004) A common set of gene regulatory networks links metabolism and growth inhibition. Mol Cell 16(3), 399-411.

12. Vartiainen, M.K., Guettler, S., Larijani, B. and Treisman, R. (2007) Nuclear actin regulates dynamic subcellular localization and activity of the SRF cofactor MAL. Science 316(5832), 1749-52.

Text: p. 45-50, Chapter 4, p. 485-486, p. 490-509.

7. October 16 EXAM

The second half of the course will devote two sessions to each of three topics, as below. The accent in these classes is on the use of genetics and model systems to find out how signaling systems work to serve specific biological needs. Most of the work and learning is done outside the classroom by careful and critical reading of prescribed reviews and research papers. The precise papers to be covered will be posted later during the semester.

For 2003 the topics were:

8. & 9. Yeast pheromone and other MAP kinase pathways

10. & 11. TGF-beta family pathways

12. & 13. Wnt signaling pathways