|David J. Gross
Associate Professor of Biochemistry and Molecular Biology, University of Massachusetts
Ph.D.: University of Illinois
Cell Surface Receptor Signaling
We primarily study the epidermal growth factor receptor (EGFR), a member of the tyrosine kinase receptor family. This 170 kDa receptor has an extracellular ligand binding domain, a single transmembrane spanning region, and an intracellular domain containing the tyrosine kinase and a regulatory subdomain. Within the regulatory region are five tyrosines that, when transphosphorylated by other EGFR, become SH2 docking sites for various signaling molecules. The EGFR is also known to be an actin binding molecule.
We employ quantitative fluorescence imaging, electrophysiology, recombinant DNA techniques, and biochemistry in our studies. We are working on effects of point mutations within the actin-binding domain of the EGFR on cellular endpoints such as control of EGFR ligand affinity, internalization, cell surface mobility and cytoskeletal interactions. We have made a green fluorescent protein-EGFR fusion protein that is useful for following EGFR processing (see figure). Other studies include examination of the role of EGFR on oocyte in vitro maturation and synthesis of a polyelectrolyte-EGF that may be useful in disrupting the endocytic pathway.
A.C. Yvon, D.J. Gross and P. Wadsworth (2001) Antagonistic forces generated by yosin II and cytoplasmic dynein regulate microtubule turnover, movement, and organization in interphase cells Proc. Natl. Acad. Sci. USA 98, 8656-8661.
M.R. Holbrook, L.L. Slakey and D.J. Gross (2000) Thermodynamic Mixing of Molecular States of the Epidermal Growth Factor Receptor Modulates Macroscopic Ligand Binding Affinity Biochem. J. 352, 99-108.
Holbrook, M.R., O'Donnell, Jr., J.B., Slakey, L.L. and Gross, D.J. (1999) Epidermal Growth Factor Internalization Rate is Regulated by Negative Charges near the SH2 Binding Site Tyr992. Biochemistry 38, 9348-9356.
Hill, J.L., Hammar, K., Smith, P.J.S. and Gross, D.J. (1999) Stage-Dependent Effects of Epidermal Growth Factor on [Ca2+] Efflux in Mouse Oocytes. Molec. Reprod. Devel. 53, 244-253.
Mahoney, M.G., Slakey, L.L., Benham, C.D. and Gross, D.J. (1998) Time course of the initial [Ca2+]i response to extracellular ATP in smooth muscle depends on [Ca2+]e and ATP concentration. Biophys. J., in press.
Chung, J.C., Sciaky, N. and Gross, D.J. (1997) Heterogeneity of epidermal growth factor binding kinetics on individual cells. Biophys. J. 73, 1089-1102.
Chung, J.C., Gross, D.J., Opsahl-Ong, L.R., Thomas, J.L. and Tirrell, D.A. (1996) pH-sensitive, cation-selective channels formed by a simple synthetic polyelectrolyte in artificial bilayer membranes. Macromolecules 29, 4636-4641.