The common human GNB3 825C > T variant, which is present in 50% of the world’s chromosomes, has previously been shown to predispose individuals to hypertension, cardiac and neural disorders. This variant causes the production of a stable and gain of function protein Gβ<sub>3S</sub>- This thesis describes the discovery of a novel D153del mutation that produces an unstable, loss of function, protein Gβ<sub>3D </sub> in the recessively inherited, retinopathy globe enlarged (rge) chickens. This thesis also demonstrates that the normal Gβ<sub>3</sub> downstream phosphorylation signalling pathways are significantly altered in a tissue specific manner in rge chicken organs and in a human GNB3 825TT lymphoblast cell line. In rge tissues expressing Gβ<sub>3D</sub> protein, the cAMP induced GRK2 phosphorylation activity is significantly altered. Moreover MAPK1 (ERK2) phosphorylation is significantly decreased compared to normal tissues. In contrast human 825TT cell lines expressing the Gβ<sub>3S</sub> protein, showed enhanced cAMP induced GRK2 and MAPK (ERK1 and ERK2) phosphorylation activity. These results confirm previous findings of 825C > T Gβ<sub>3</sub> studies, that Gβ<sub>3S</sub> is indeed a hyper-activating structural variant, in contrast to the D153del Gp3D is a classical recessively inherited non-functional mutation.
| Identifer | oai:union.ndltd.org:bl.uk/oai:ethos.bl.uk:651288 |
| Date | January 2008 |
| Creators | Tummala, Hemanth |
| Contributors | Lester, Douglas |
| Publisher | Abertay University |
| Source Sets | Ethos UK |
| Detected Language | English |
| Type | Electronic Thesis or Dissertation |
| Source | https://rke.abertay.ac.uk/en/studentTheses/baf432d1-5f39-43bd-9e47-abc3813985ad |
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