6 postdoctoral fellows, 6 graduate students
The long term research objective of the Cantley lab is to understand the biochemical basis for mammalian cell growth regulation and transformation. In particular, we are trying to understand the structural basis for specificity and regulation of protein kinases and phosphatidylinositol kinases that have been implicated in mammalian cell growth control. This research involves the cloning and expression of sufficient quantities of these proteins for in vitro studies. In addition, mutant forms of the proteins are added back to cells to determine the role of the proteins in cellular responses. Recently, we have developed a new `oriented peptide library' technique that allows us to quickly determine the optimal peptide sequence for binding to specific catalytic or regulatory sites of protein kinases. This approach provides rapid results that are providing new insights into the structural basis for protein/protein interactions.
Songyang, Z., Shoelson, S.E., Chadhuri, M., Gish, G.., Pawson, T., Haser, W.G., King, F., Roberts, T., Ratnofsky, S., Lechleider, R.J., Neel, B.G., Birge, R.B., Fajardom, J.E., Chous, M.M., Hanafusa, H., Schaffhausen, B. and Cantley, L.C. (1993) SH2 domains recognize specific phosphopeptide sequences. Cell 72:767-778.
Songyang, Z., Shoelson, S.E., McGlade, j., Olivier, P., Pawson, T., Bustelo, R.X., Barbacid, M., Sabe, H., Hanafusa, H., Yi, T., Ren, R., Baltimore, D., Ratnofsky, S., Feldman, R.A. and Cantley, L.C. (1994) Specific motifs recognized by the SH2 domains of Csk, 3BP2, fps/fes, Grb-2, SHPTP1, SHC, Syk and Vav. Mol. Cell. Biol. 14:2777-2785.
Marengere, L.E.M., Songyang, Z., Gish, G.D., Schaller, M.D., Parsons, J.T., Stern, M.J., Cantley, L.C. and Pawson, T. (1994) SH2 domain specificity and activity modified by a single residue. Nature 369:502-505.
Carraway, K.L. III and Cantley, L.C. (1994) A neu contact for Erb B3 and Erb B4: Receptor heterodimerization provides diversity in growth factor signaling. Cell 78:5-8.
Yoakim, M., Hou, W., Songyang, Z., Liu, Y., Cantley, L.C. and Schaffhausen, B. (1994) Genetic analysis of a I 3-kinase SH2 domain reveals determinants of specificity. Mol. Cell. Biol. 14:5929-5938.
Songyang, Z., Blechner, S., Hoaglard, N., Hoekstra, M.F., Piwnica-Worms, H. and Cantley, L.C. (1994) A novel oriented peptide library technique for determining optimal substrates of protein kinases. Current Biology 4:973-982.
Toker, A., Meyer, M., Reddy, K.K., Falck, J.R., Aneja, R., Aneja, S., Parra, A., Burns, D.J., Ballas, L.M. and Cantley, L.C. (1994) Activation of protein kinase C family members by the novel polyphosphoinositides PtdIns-3,4-P2 and PtdIns-3,4,5-P3. J. Biol. chem. 269:32358-32367.
Songyang, Z., Carraway, K.L. III, Eck, M.J., Harrison, S.C., Feldman, R.A., Mohammodi, M., Schlessinger, J., Hubbard, S.R., Mayer, B.J. and Cantley, L.C. (1995) Catalytic specificity of protein-tyrosine kinases is critical for selective signaling. Nature 373:536-539.
Rameh, L. E., Chen, C.-S., and Cantley, L. C. (1995). Phosphatidylinositol-3,4,5-P3 Interacts with SH2 Domains and Modulates Phosphoinositide 3-kinase Association with Tyrosine-Phosphorylated Proteins. Cell 83:821-830.