I am interested in understanding some of the factors involved in the expression and function of guanine nucleotide regulatory proteins (G proteins). Identifying the mechanisms by which G protein expression is regulated is important because abnormalities in the function of some of these proteins have been implicated in hypertension, non-insulin dependent diabetes mellitus (NIDDM), endocrine tumors, and obesity. As my thesis project, I will test the hypothesis that the alpha subunit of the G protein, Gi2 (Gi2alpha) translocates from the plasma membrane to the nucleus when cells differentiate under the stimulus of certain differentiation-inducing agents or mitogens. Swiss 3T3 and U937 cells will be used as the experimental models to study this phenomenon. Subcellular fractionation coupled with Western blotting of fractions as well as visualization of Gi2alpha by indirect immunofluorescence and laser scanning confocal microscopy (LSCM) will be used to monitor the translocation. If translocation is demonstrated, I will explore the biological significance of this phenomenon. My hypothesis is that the translocation may be related to phosphoinositol metabolism in the nucleus which subsequently influence such nuclear events as cell division.
