Characterization of Ligand-Induced Endocytosis of EGF - Receptors.
Annual rept. 9 May 95-8 May 96,
SCRIPPS RESEARCH INST LA JOLLA CA
Pagination or Media Count:
We have made progress this year in engineering and using a cell line that is conditionally defective in receptor-mediated endocytosis to directly assess the role of endocytosis in controlling cellular responses to activated EGF-R. We find, not surprisingly, that cells defective in endocytosis show a stronger proliferative response to FGF than wt cells. Surprisingly, we find that some EGF-R signaling pathways, specifically the MAP kinase activation and EGF-R phosphorylation itself are reduced in mutant cells relative to wt cells. Thus, endocytosis plays a role in specifying EGF-R signaling events, not just in attenuating them. Given the importance of endocytosis in EGF-R signaling our discovery, that Rho-family GTPases which are activated in response to growth factors are negative regulators of receptor-mediated endocytosis, may have important implications or control of receptor signalling. Finally we have begun to examine the role of epsl5, a tyrosine kinase substrate of the EGF-R which binds constitutively to the AP2 endocytic coat proteins, on endocytosis of EGF-R using our in vitro assay.
- Genetic Engineering and Molecular Biology
- Medicine and Medical Research