Danny Brower
Professor of Molecular & Cellular Biology and Biochemistry
& Molecular Biophysics
Ph.D., University of Colorado
Integrin function and structure.
Research Interests
Our research focuses on integrin structure and function, using as a model system the PS integrins of Drosophila. Like other members of the integrin family, each PS integrin is composed of an alpha and beta subunit, both of which are large transmembrane glycoproteins. Like most vertebrate integrins, the fly PS integrins are receptors for extracellular matrix proteins. In humans, integrins are involved in a wide variety of developmental and other processes. Integrins are components of the signaling pathways that regulate cell proliferation, and they are intimately involved in the changes that allow tumor cells to spread in the body. Also, integrins on platelets mediate blood clotting, both normally and during pathological events such as heart attacks. Thus elucidation of basic mechanisms of integrin function is a high priority to the biomedical research community.
We work in Drosophila in order to combine sophisticated genetic
approaches with the more standard cell biological methods available to workers in vertebrate systems. The genes for the various fly integrin subunits are known, as well as genes for a number of extracellular integrin ligands, and we have made transgenic animals that express specific integrins or ligands under the control of inducible promoters. We use combinations of mutant and transformed animals to probe integrin functions in situ, including screens for suppressors and enhancers of genetically sensitized animals, in order to identify proteins that function upstream and downstream of integrins. We also are pursuing genetic and molecular approaches, both in whole animals and cell culture, designed to dissect structure-function relationships of integrin heterodimers.
Select Publications
Any link on the below references will take you off of the BMCB site and to an abstract of that particular paper.
Bunch, T.A., T.L. Helsten, T.L. Kendall, N. Shirahatti, D. Mahadevan, S.J. Shattil, and D.L. Brower. 2006. Amino acid changes in Drosophila aPS2bPS integrins that affect ligand affinity. Journal of Biological Chemistry 281: 5050-5057.Jannuzi, A.L., T.A. Bunch, R.F. West, and D.L. Brower. 2004. Identification of integrin beta subunit mutations that alter heterodimer function in situ. Molecular Biology of the Cell 15: 3829-3840.
Bunch, T.A., Miller, S.W., and Brower, D.L. 2004. Analysis of the Drosophila betaPS subunit indicates that regulation of integrin activity is a primal function of the C8-C9 loop. Experimental Cell Research 294: 118-129.
Miller, S.W., Hayward, D.D., Bunch, T.A., Miller, D.J., Ball, E.E., Bardwell, V.J., Zarkower, D. and Brower, D.L. (2003) A DM domain protein from a coral, Acropora millepora, homologous to proteins important for sex determination. Evolution & Development 5: 251-258.
Brower, D.L. 2003. Platelets with wings: The maturation of Drosophila integrin biology. Current Opinion in Cell Biology 15: 607-613.
Baker, S.E., J.A. Lorenzen, S.W. Miller, T.A. Bunch, A.L. Jannuzi, M.H. Ginsbrerg, L.A. Perkins, and D.L. Brower. 2002. Genetic interaction between integrins and moleskin, a gene encoding a Drosophila homologue of Importin-7 (DIM-7). Genetics 162: 285-296.
Jannuzi, A.L., T.A. Bunch, M.C. Brabant, S.W. Miller, L. Mukai, M. Zavortink, and D.L. Brower. 2002. Disruption of the C-terminal cytoplasmic domain of the beta-PS integrin subunit has dominant negative properties in developing Drosophila. Molecular Biology of the Cell 13: 1352-1365.
Schmitt, D., and D.L. Brower. 2001. Intron dynamics and the evolution of integrin beta-subunit genes: Maintenance of an ancestral gene structure in the coral, Acropora millepora. Journal of Molecular Evolution 53: 703-710.
Lorenzen, J.A., S.E. Baker, F. Denhez, M.B. Melnick, D.L. Brower, and L.A. Perkins. 2001. Nuclear import of activated D-ERK by DIM-7, an Importin family member encoded by the gene moleskin. Development 128: 1403-1414.
Contact Information
| Mailing: Danny Brower, Professor Department of Molecular & Cellular Biology University of Arizona Arizona Cancer Center 0977B P. O. Box 245024 Tucson, AZ 85724-5024 |
Telephone: 520-621-7563 (Office) 520-621-3869 (Lab) Fax: Email: |
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