Boulton T.G., Nye S.H., Robbins D.J., Ip N.Y., Radziejewska E., Morganbesser
S.D., DePinho R.A., Panayotatos N., Cobb M.H., and Yancopoulos G.D. ERKs: A
family of protein-serine/threonine kinases that are activated and tyrosine
phosphorylated in response to insulin and NGF. Cell, 65, 663-675, 1991.
Robbins D. J., Cheng M., Zhen E., Vanderbilt C. A., Feig L. A., Cobb M.H.
Evidence for a Ras-dependent extracellular signal-regulaetd protein kinase
cascade. Proc. Natl. Acad. Sci., 89, 6924-6928, 1992.
Zhang, F., Strand, A., Robbins, D., Cobb, M. H., and Goldsmith, E. J.
Atomic structure of the MAP kinase ERK2 at 2.3 A resolution. Nature 367,
704-11, 1994.
Robbins, D. J., Nybakken, K. E., Kobayshi, R., Bishop, J. M., and Therond,
P. Hedgehog elicits signal transduction by means of a large complex
containing the kinesin related protein cos2. Cell 90, 225-234, 1997.
Zeng, X, Goetz,J., Suber, L., Schrenier, C., Scott, W., and Robbins, D.J.. A
Freely Diffusible form of Sonic Hedgehog Mediates Long-range Signaling.
Nature 7;411(6838):716-20, 2001
Ogden, S.K., Ascano, M. Jr, Stegman, M.A., Suber, L., Hooper, J.E. and
Robbins, D.J. Identification of a functional interaction between the
transmembrane protein Smoothened and the kinesin related protein Costal2.
Current Biology, in press.
Stegman, M.A., Ascano, M., Goetz, J., Ogden, S., and Robbins, D.J. Costal2
associates directly with endosomal membranes. J Biol Chem, in press.
Research / Lab Interests
Elucidating the Mechanism of Action of the Morphogen Sonic
Hedgehog.
The Hedgehog (Hh) signal transduction pathway plays a critical role in both early development and in cancer. In fact, mutations in components of this pathway underlie a number of human developmental disorders, and contribute to a broad range of malignancies. Hh was first identified as a Drosophila gene required during early embryogenesis, by the pioneering work of Nüsslein-Volhard and Wieschaus. Subsequent work has also implicated Hh, which is a secreted protein, in the patterning of the imaginal discs that go on to form the various structures in the adult fly. In vertebrates, Hh family members are also involved in the patterning of a diverse array of structures, such as the limb bud, floorplate, and motor neurons. The phenotypes of individuals with the developmental disorder known as Gorlin's syndrome, in which the human Hh receptor is mutated, are consistent with a Hh requirement in the development of these structures. Besides numerous developmental abnormalities, individuals afflicted with Gorlin's syndrome have an inherited predisposition to a variety of tumor types. Components of the Hh signaling pathway are also found mutated in sporadic forms of these same tumors, underlying the importance of the Hh pathway in human oncogenesis. The mechanism by which this pathway contributes to either oncogenesis or development remains unknown. My research program is focused on elucidating Hh?s mechanism of action. This goal is approached in two ways: 1) elucidating the production and presentation of the Hh ligand, and 2) dissecting the signaling pathway downstream of the Hh receptor. We are studying this pathway in both developmental and pathological settings, making our research highly complementary and mutually supporting. Such an approach will more rapidly decipher the mechanism by which the Hh pathway contributes to both human oncogenesis and development.
