Abstract: Award DAMDl7-99-l-9367 seeks to understand the role of membrane trafficking in Epidermal Growth Factor Receptor (EGFR) signal transduction. We have been using a tissue culture model system (HeLa cells) to isolate the activated EGFR at distinct stages in the endocytic pathway. Our research has focused on rab5, a small molecular weight GTPase, implicated in the biogenesis of the early endosome. Mutations to modulate the guanine nucleotide binding properties of this protein have been reported for constitutively internalized receptors, but little is known about its role in EGFR endocytic trafficking. In the past year, we have published our finding that constitutively active rab5 (rab5(Q79L)) induced enlarged early endosomes without any consequence on receptor or membrane trafficking (Ceresa, et. al, JBC 276 p. 9649) . Our continued pursuit on this avenue of research has shown that the dominant negative form of rab5 (rab5(S34N)) does not block EGFR endocytosis, but may block entry on the EGFR into the early endosome. We are in the process of developing a biochemical assay to confirm our immunofluorescence observations. Additionally, we are in the process of developing a model system to examine the role of endocytic trafficking on signaling by other members of the ErbB family, namely ErbB2.
| Limitations: |
 APPROVED FOR PUBLIC RELEASE |
| Description: |
Annual summary rept. 1 Jul 2000-30 Jun 2001 |
| Pages: |
24 |
| Report Date: |
JUL 2001 |
| Contract Number: |
DAMD17-99-1-9367 |
| Report Number: |
A804693 |
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