Study of the Regulation of erbB Signaling by Receptor-mediated Endocytosis
Annual rept. 1 May 1999-30 Apr 2000
PENNSYLVANIA UNIV PHILADELPHIA
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Endocytosis of erbB receptors is an important regulator of erbB receptor signaling. Given that abnormal erbB signaling may lead to cellular transformation, it is important to understand the factors that determine its regulation. ErbB-2, the erbB receptor that forms heterodimers with all other erbB receptors, is widely implicated in the development of breast cancer. ErbB-2 does not have a known ligand and has an intrinsically slow rate of endocytosisdown-regulation. An attractive hypothesis is that erbB-2 associates with other erbB receptors, forming more persistent signaling complexes because they are down- regulated slower than erbB homodimers. Prolonged, potentiated erbB signaling is thought to contribute to cellular transformation and cancer. It is the goal of this project to study and establish a link between regulation of endocytosisdown-regulation and abnormal signaling that may contribute to cancer development.
- Anatomy and Physiology
- Medicine and Medical Research