A novel type of G protein heterodimer: The Gbeta5-RGS complex
Date of Award
Doctor of Philosophy (Ph.D.)
Molecular and Cellular Pharmacology
First Committee Member
Irene Litosch, Committee Chair
The fifth member of G protein beta subunit family, Gbeta5, has been previously shown to bind to a subfamily of regulators of G protein signaling (RGS) including RGS6, RGS7, RGS9 and RGS11. The interaction between Gbeta5 and RGS proteins challenged the belief that all Gbeta subunits exist as an obligatory heterodimer with G protein gamma subunits. To determine if Gbeta5 exists exclusively with RGS proteins or also with Ggamma subunits, Gbeta5 from brain extracts was partially purified and its native binding partners observed. The results demonstrated that unlike other Gbeta subunits, Gbeta5 does not bind to Ggamma subunits in vivo, and instead is detected only as a heterodimer with a subfamily of RGS proteins. Gbeta5-RGS7 was shown to exist in both cytosolic and membrane extracts from native tissues. This novel Gbeta5-RGS heterodimer is the only form detected in cells, as monomeric forms of both proteins are rapidly degraded. Furthermore, the Gbeta5-RGS7 dimer acts to attenuate Galphaq signaling in cells due to a direct protein-protein interaction of the dimer with Galphaq.
Biology, Molecular; Health Sciences, Pharmacology
Witherow, Dennis Scott, "A novel type of G protein heterodimer: The Gbeta5-RGS complex" (2003). Dissertations from ProQuest. 1987.