Dr. Rachel Sterne-Marr

Professor of Biology

Director of the Biochemistry Program

B.S. in Biology, University of California, Los Angeles (1983)
Ph.D. Biochemistry, University of California, Berkeley (1989)

Postdoctoral studies at Scripps Research Institute, Thomas Jefferson University and 
Merck, Sharp & Dohme Research Laboratories (1989-1995) 
Current Courses: Biochemistry, Molecular Genetics, Chemical Communications, Senior Research

Teaching Interests

  • In general, promoting an understanding and appreciation for the chemical basis of biological phenomena
  • Biochemistry Lecture: Protein Structure/Function, Enzymology, Drug Design, Molecular Visualization (Jmol/PyMol), Metabolism, and Cell Signaling
  • Biochemistry Lab: Titration, Enzymology, Protein Purification (Ion Exchange Chromatography), and Independent Projects (Affinity Chromatography, Enzymology of Biofuel Production, Clinical Assay Design, Insulin Signaling/Immunoblotting)
  • Molecular Genetics: Biochemistry of Nucleic Acids, Regulation of Gene Expression, Recombinant DNA/Biotechnology, Genetic Screens, Reverse Genetics, Genomics, Bioinformatics, Cancer Genetics 
Undergraduate Research

I am committed to developing career scientists and providing opportunities for undergraduate research. With the assistance of three National Science Foundation research grants (1997-2013), I have mentored ~70 research students in the last eighteen years.  In addition, in collaboration with other Siena science faculty, I have secured funding to support undergraduate research training (NSF STEM/Tech Valley Scholars and Clare Booth Luce Fellowships) and to promote the participation of women and under-represented individuals in science, technology, engineering and mathematics. Fifteen former undergraduate students are co-authors in JBC, Biochemistry, and Methods in Enzymology papers from my lab.

Research Interests

My research interests lie at the intersection of protein structure/function relationships and the regulation of cellular processes. For nearly twenty years, I have been intrigued by the molecular interactions that modulate cell surface receptor signaling. Specifically, I study activation of G protein-coupled receptor (GPCR) kinases (GRKs) by their phosphoacceptor targets, the ligand-activated GPCRs. This regulatory circuit is assessed using GRK and receptor mutagenesis, in vitro kinase assays, intact cell phosphorylation assays, and BRET-based receptor recruitment assays. Our work is facilitated by a long-time collaboration with John Tesmer, a crystallographer at the University of Michigan, and a recently established collaboration with Michel Bouvier, a leading BRET expert, and his postdoc Alex Beautrait at the University of Montréal.

Selected Publications (former Siena students in bold)

  • Nance, M. R., Kreutz, B., Tesmer, V. M., Sterne-Marr, R., Kozasa, T., and Tesmer, J. J. G. (2013).  Structural and Functional Analysis of the Regulator of G Protein Signaling 2 (RGS2)-Gαq Complex, Structurein press
  • Sterne-Marr, R., Baillargeon, A.I., Michalski, K.R, Tesmer, J.J.G. (2013) Purification and Structural and Functional Analysis of G Protein-Coupled Receptor Kinases.  Methods in Enzymology, in press
  • Sterne-Marr, R., Leahey, P.A., Bresee, J.E., Dickson, H.M., Ho, W., Ragusa, M.J., Donnelly, R.M., Amie, S.M., Krywy, J.A., Brookins-Danz, E.D., Orakwue, S.C., Carr, M.J., Yoshino-Koh, K., Li, Q., and Tesmer, J. J. G. (2009) GRK2 Activation by Receptors: Role of the Kinase Large Lobe and Carboxyl-Terminal Tail, Biochemistry, 48:4285-4293.
  • Lodowski D.T., Barnhill J.F., Pyskadlo R.M., Ghirlando R., Sterne-Marr R., Tesmer, J.J.  (2005)  The role of G beta gamma and domain interfaces in the activation of G protein-coupled receptor kinase 2.  Biochemistry 44:6958-70.
  • Sterne-Marr, R., Tesmer, J.J.G., Day, P.W., Stracquatanio, R.P., Cilente, J.-A., O’Connor, K. E., Pronin, A.N., Benovic, J.L., and Wedegaertner, P.B.  (2003) GRK2/Gαq/11 Interaction:  A Novel Surface on an RGS Homology Domain for Binding Gα Subunits.  J Biol. Chem. 278:6050-58.
  • Sterne-Marr, R., Dhami, G.K., Tesmer, J.J.G., and Ferguson, S.S.G.  (2004)  Characterization of GRK2 RH Domain-dependent Regulation of GPCR Coupling to Heterotrimeric G Proteins.  Methods in Enzymology 390:310-36.
  • Day, P.W., Tesmer, J.J.G., Sterne-Marr, R., Freeman, L.C., Benovic, J. L. and Wedegaertner, P.B. (2004) Characterization of the GRK2 binding site of Gαq, J. Biol. Chem. 279:53643-52.
  • Sterne-Marr, Gurevich, V.V., Goldsmith, P., Bodine, R.C, Sanders, C. Donoso, L.A., and Benovic, J.L. (1993)  Polypeptide variants of beta-arrestin and arrestin3.  J. Biol. Chem., 268:15640-15648.  
  • Sterne-Marr, R., Blevitt, J.M., and Gerace, L.  (1992) O-linked glycoproteins of the nuclear pore complex interact with a cytosolic factor required for nuclear protein import.  J. Cell Biol. 116:271-280.
Adam, S. A., Sterne Marr, R., and Gerace, L.  (1990) Nuclear protein import in permeabilized mammalian cells requires soluble cytoplasmic factors.  J. Cell Biol. 111:807-818. 

  • Schafer, W. R., Kim, R., Sterne, R., Thorner, J., Kim, S.-H. and Rine, J.  (1989) Genetic and pharmacological suppression of oncogenic mutations in RAS genes of yeast and humans.  Science 245:379-385.    
GRK2 Kinase Domain Residues Required for GPCR-mediated Activation. The GRK2 kinase domain was modeled in a closed conformation based on an activated structure of PKA (PDB 1L3R). To map a GPCR docking site, two regions of the kinase domain were targeted for mutagenesis: the large lobe and the C-tail. To indicate the expected position of the phosphoacceptor binding site, the phosphoacceptor sequence of rhodopsin (peptide C; grey spheres) was docked onto the structure using the structure of the glycogen synthase kinase 3β peptide bound to protein kinase B as a guide (PDB code 1O6K). Nearby residues that could interact with other regions of the receptor (His280, Tyr281, Gln285, Ser284, His394, Lys395, and Lys397) were substituted with alanine. The AST of GRK2 has also been implicated in receptor interaction but residues Glu476-Leu499 have been unstructured in all crystals of GRK2 reported thus far. However, a nearly fully ordered AST loop (black backbone) was observed in GRK1. This structure was mapped onto GRK2 to provide an estimate of the locale of amino acids in the AST. Pro473, Glu476, Val477, Asp481, Phe483, Asp484, Ile485, Phe488, Glu490, Gly495 and Leu499 in the AST were selected for site-directed mutagenesis. Substituted residues that showed diminished capacity to phosphorylate receptor and at least some of the non-receptor substrates have carbon atoms colored magenta, whereas those that did not have significant effects on rhodopsin phosphorylation have carbons colored yellow. (Inset) A space-filling model of GRK2 at the plasma membrane with RH domain shown in purple and magenta, and the PH domain is colored brown. We speculated that the cleft between the lipid bilayer and the kinase large lobe could serve to accommodate the intracellular loops and carboxyl tail of a GPCR. Mutated residues in the kinase domain are shown as yellow spheres. From Sterne-Marr et al., 2009.