G-protein signaling underlies the mechanism of half of all prescription drugs, yet remains a hot-bed of medical research. Tubulin, although a cytoskeletal protein, activates Gsalpha, Gi1alpha and Gqalpha by direct transfer of GTP. Also, Gs alpha activates the tubulin GTPase activity and modulates microtubule dynamics. There is biochemical, microscopic, signaling and molecular modeling evidence supporting this mechanism. Physiologically, G-protein-tubulin interactions modulate cell signaling and are required for cellular differentiation and neurite outgrowth.
My interest is whether Gs alpha differentially interacts with beta-tubulin isotypes. Differences between tubulin isotypes have been mostly overlooked (partly due to technical reasons), but it is likely that different beta-isotypes have distinct functions. Indeed, beta-III tubulin is upregulated in glial and neuroendocrine tumors and correlates with lack of differentiation and poorer clinical prognosis. It is possible that differential interaction of Gs alpha with tubulin isotypes may underlie the correlation between beta-III tubulin and tumor anaplasia.
I am investigating the interaction of Gs alpha with different beta-tubulin isotypes in vitro at the level of binding affinity, as well as functional differences. Specifically, I am interested in whether
Later on, these studies can be taken to the clinical front. One of my long-term interests to investigate differences in signaling between tumors and normal tissues in relationship to Gs alpha-tubulin interaction.