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Title: Endofin is a novel component in EGR/EGFR oncogenic signaling
Authors: TOY WEIYI
Keywords: Endofin, EGF, EGFR, tyrosine phosphorylation, endosome, MAPK
Issue Date: 4-Jan-2010
Citation: TOY WEIYI (2010-01-04). Endofin is a novel component in EGR/EGFR oncogenic signaling. ScholarBank@NUS Repository.
Abstract: Endofin is an endosomal protein that localizes to the early endosomes. It is characterized by a zinc-finger domain, referred to as the FYVE domain. This domain targets Endofin to the early endosomes by binding to the phosphatidylinositol 3-phosphate within the endosomal membrane. Endofin functions as a regulator of specific signaling pathways, such as BMP and TGF-ß signaling, whereby it plays the role of an adaptor. Furthermore, it has been identified as a novel tyrosine phosphorylation target downstream of EGFR. To date, there have only been a few functional studies published on Endofin and consequently our understanding of Endofin¿s functions is very limited, especially with respect to EGFR signaling. In this study, an attempt was made to map the signaling events associated with Endofin following activation of EGFR with EGF. Tyrosine phosphorylation of Endofin was shown to be dependent on clathrin-dependent endocytosis of EGFR and EGFR activity. Phosphatidylinositol 3-kinase activity and FYVE domain-mediated localization of Endofin to early endosomes were found to be necessary for the tyrosine phosphorylation of Endofin. Tyrosine 515 was identified as a major phosphorylation site on Endofin however disruption of phosphorylation at Y515 neither affects Endofin¿s localization nor its co-localization with EGFR at the endosomes. Instead, the abrogation of Y515 phosphorylation and the mislocalization of Endofin were found to enhance the amplitude of the MAPK cascade and increase cell proliferation, suggesting a possible role of Endofin in the modulation of MAPK pathway. Collectively, this study has identified a novel signaling cascade involving EGFR, PI3K, Endofin and MAPK in the EGFR signaling network.
Appears in Collections:Ph.D Theses (Open)

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