Department of Biochemistry

Steven G. Graber, Ph.D.

Ph.D. - University of Vermont, 1986
Postdoctoral Fellowship - University of Virginia

Associate Professor
Department of Biochemistry
West Virginia University
P.O. Box 9142
Morgantown, WV 26506
Phone: (304) 293-2305
Fax: (304) 293-6846
Email: sgraber@wvu.edu

Research:

The laboratory is interested in contributing to the understanding of the molecular mechanisms underlying G protein mediated signal transduction.

Description of Research:

A striking feature of G protein coupled signaling pathways is the large number of distinct subtypes identified for each component. At the biochemical level significant contributions in this area can be made by developing the ability to employ purified components of signal transduction pathways in reconstitution paradigms. A baculovirus expression system has been used to produce individual components of various signal transduction pathways. The primary focus has been on the potential role for specific combinations of G proteins as determinants of selectivity in signaling pathways. Among the issues being addressed are:

1. whether G protein heterotrimers are formed selectively from distinct a and bg subunits;

2. whether specific a or bg subunits are determinants of G protein coupling to specific receptors;

3. which specific domains on the subunit interact with receptors;

4. whether the subunit composition of the G protein coupled to a given receptor affects the ability of the receptor to modulate the activity of its' target effector.

Dr. Graber is a member of the Interdepartmental Graduate Program in Neuroscience.

Selected Publications:

• Slessareva JE, Ma H, Depree KM, Flood LA, Cabrera-Vera TM, Hamm HE and Graber SG: "Closely related G protein coupled receptors use multiple and distinct domains on G protein α subunits for selective coupling" J. Biol. Chem. 278:50530 - 50536 (2003).

• Ma H., Peterson YK, Bernard ML, Lanier SM and Graber SG: "Influence of Cytosolic AGS3 on Receptor-G Protein Coupling" Biochemistry 42: 8085-8093 (2003).

• Slessareva JE and Graber SG: "Reconstitution Reveals Additional Roles for N- and C-Terminal Domains of G in Muscarinic Receptor Coupling" Biochemistry 42: 7552-7560 (2003).

• Cabrera-Vera TM, Thomas TO, Vanhauwe J, Depree KM, Graber SG and Hamm HE: "Dissecting receptor-G protein specificity using G alpha chimeras" Meth. Enzymology 344:69-81 (2002).

• Peterson YK, Hazard S, Graber SG and Lanier SM: "Identification of structural features in the GPR motif required for regulation of heterotrimeric G-proteins" J. Biol. Chem. 277:6767-6770 (2002).

• Cordeaux Y, Nickolls SA, Flood LA, Graber SG and Strange PG: "Influence of G-protein subtype on signaling through the D2long dopamine receptor" J. Biol. Chem. 276:28667-28675 (2001).

• Peterson YK, Bernard ML, Ma H, Hazard S, Graber SG and Lanier SM: "Stabilization of the GDP-bound Conformation of Gi a by a Peptide Derived from the G-protein Regulatory Motif of AGS3" J. Biol. Chem. 275: 33193-33196 (2000).

• Kazmi MA, Snyder LA, Cypess AM, Graber SG and Sakmar TP:  "Selective Reconstitution of Human D4 Dopamine Receptor Variants with Gi Subtypes" Biochemistry 39: 3734-3744 (2000).