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Title: The diverse effects of CD98 in terms of its structural/functional relationship
Author: Collis, E. A.
Awarding Body: University of Edinburgh
Current Institution: University of Edinburgh
Date of Award: 2005
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CD98 is a transmembrane heterodimeric protein which is highly expressed on the surface of tumour cells irrespective of tissue of origin. This investigation has demonstrated that CD98 constitutively and specifically associates with β1 integrins and that over expression of the CD98 heavy chain promotes both anchorage-independent and serum-independent growth. This oncogenic activity is dependent on phosphoinositol-3-OH kinase stimulation and the level of surface expression of CD98. Using chimeras of the CD98 heavy chain and the Type II membrane protein CD69, I have shown that the transmembrane domain is necessary and sufficient for integrin association. Amino acids 82-87 in the putative cytoplasmic/transmembrane region appear to be critical for the oncogenic potential of CD98 and provide a novel mechanism for tumour promotion by integrins. This study presents a hypothesis to explain how high expression of CD98 causes transformation in human cancers. The transmembrane association of CD98 and β1 integrins may provide a unique target for therapeutic intervention in cancer. The Neural cell adhesion molecule (NCAM), is a membrane associated glycoprotein of the Ig superfamily which is highly expressed in small cell lung cancer and has been shown to activate integrins in a number of cellular systems. This study has shown that CD98 and NCAM and NCAM and β1 colocalise and synergise to increase oncogenic signalling by CD98. Together these findings suggest that NCAM, CD98 and β1 may form a membrane signalling complex which senses local environment and induces a cytoplasmic signalling cascade leading to transformation.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available