Fas Ligand (FasL) binds to the Fas receptor to induce apoptosis or activate other signaling pathways. FasL can also transduce "reverse signals" and thus participate in bidirectional signaling. The FasL intracellular domain contains consensus sequences for phosphorylation and a proline rich protein interaction domain. This latter region of FasL has previously been implicated in FasL reverse signaling and regulation of FasL surface expression. In this report, we sought to identify novel FasL interacting proteins to help understand signaling through and trafficking of this death factor. Using mass spectrometry, we identified sorting nexin 18, adaptin beta, Grb2, PACSIN2 and PACSIN3 as FasL interacting proteins. RNAi mediated knockdown of Grb2 significantly reduced the surface expression of FasL and increased its expression intracellularly. Our data show that Grb2 controls the subcellular localization of FasL. All other proteins identified in our screen could be classified as trafficking-associated proteins, highlighting the complex regulation of the surface expression of this death factor.
| Identifer | oai:union.ndltd.org:LACETR/oai:collectionscanada.gc.ca:QMM.100212 |
| Date | January 2007 |
| Creators | Thornhill, Peter, 1981- |
| Publisher | McGill University |
| Source Sets | Library and Archives Canada ETDs Repository / Centre d'archives des thèses électroniques de Bibliothèque et Archives Canada |
| Language | English |
| Detected Language | English |
| Type | Electronic Thesis or Dissertation |
| Format | application/pdf |
| Coverage | Master of Science (Department of Physiology.) |
| Rights | © Peter Thornhill, 2007 |
| Relation | alephsysno: 002652761, proquestno: AAIMR38437, Theses scanned by UMI/ProQuest. |
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