Receptor tyrosine kinases (RTKs) mediate transduction of extracellular signals to the interior of the cell. The oncogenic variant of the Met RTK (Tpr-Met) transforms fibroblast cells. Multiple proteins involved in activating signal transduction pathways bind the Tpr-Met protein at a single highly phosphorylated tyrosine, tyrosine 489. This tyrosine residue is essential for Tpr-Met mediated transformation, implicating one or more of these substrates in this event. The specificity of the interaction between RTKs and their substrates is determined by amino acids surrounding the phosphotyrosine residue. To determine the role of each Tpr-Met substrate in cellular transformation, I have designed Tpr-Met mutants predicted to have a unique substrate binding specificity, by altering the three amino acids immediately downstream of tyrosine 489. My results show that the in vitro optimal binding motifs predicted for various substrates may not apply in vivo to Tpr-Met.
| Identifer | oai:union.ndltd.org:LACETR/oai:collectionscanada.gc.ca:QMM.20584 |
| Date | January 1998 |
| Creators | Mahendran, Mahishini. |
| 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 Biochemistry.) |
| Rights | All items in eScholarship@McGill are protected by copyright with all rights reserved unless otherwise indicated. |
| Relation | alephsysno: 001605523, proquestno: MQ44215, Theses scanned by UMI/ProQuest. |
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