- Lauren E. Ball, Ph.D.
- Joe B. Blumer, Ph.D.
- Warren Davis Jr., Ph.D.
- Scott Eblen, Ph.D.
- Perry V. Halushka, M.D., Ph.D.
- John D. Hildebrandt, Ph.D.
- Jennifer S. Isaacs, Ph.D.
- Daniel R. Knapp, Ph.D.
- David T. Kurtz, Ph.D.
- Stephen M. Lanier, Ph.D.
- Carola A. Neumann, M.D.
- John E. Oatis, Ph.D.
- Steven A. Rosenzweig, Ph.D.
- Kevin L. Schey, Ph.D.
- Kenneth D. Tew, Ph.D., D.Sc.
- Thomas Walle, Ph.D.
- Michael J. Wargovich, Ph.D.
- Jerry G. Webb, Ph.D.
Stephen M. Lanier, Ph.D.
Professor
Cell and Molecular Pharmacology
Associate Provost for ResearchPh.D., University of Tennessee Center for Health Sciences, 1982
laniersm@musc.edu
Tel: 843-792-0442
Fax: 843-792-5110
Accessory Proteins for G-Protein Signaling Systems.
G-proteins are one of the most widely used mechanisms in nature for transducing signals from the extracellular to the intracellular environment. Accessory proteins that interact with and regulate G-proteins offer unexpected and surprising mechanisms for signal input to G-protein signaling systems.
OVERALL HYPOTHESIS: Signaling efficiency/specificity for heterotrimeric G-protein systems is determined in part by accessory proteins which regulate the efficiency and/or specificity of signal transfer from G-protein coupled receptors (GPCRs) to G-proteins, segregate a signaling complex to microdomains of the cell, regulate the basal activity of the system and/or provide alternative modes of signal input to G-protein signaling systems that operate independent of a typical GPCR.
Relative to this hypothesis our long-term objectives are to define such accessory proteins, their mechanism of regulation, their dysfunction in various diseases and their potential as therapeutic targets.
We developed a series of experimental approaches to identify such accessory proteins. One approach was based upon protein interaction strategies with receptor subdomains. A second approach was based upon the functionality of the system and was designed to identify novel proteins that directly regulate the activation state of G-protein. The latter approach led to the discovery of Activators of G-protein signaling (AGS) 1-10. AGS proteins interact with different subunits and/or conformations of heterotrimeric G-proteins and selectively regulate different types of G-proteins.
AGS and related accessory proteins provide unexpected mechanisms for regulation of the G-protein activation cycle and have opened up a new area of research related to the cellular role of G-proteins as signal transducers.
In addition to the obvious interest related to GPCR signaling, such proteins may also provide alternative binding partners for G-protein subunits that allow G-proteins to serve unexpected functions related to cell division, differentiation and organelle structure. As such, these proteins and the concepts advanced with their discovery provide unexpected avenues for therapeutic development and increased understanding of disease mechanisms.
Recent Publications | Additional Publications
Yuan C, Sato M, Lanier SM and Smrcka AV. (2007) Signaling by a non-dissociated complex of G-protein betagamma and alpha subunits stimulated by a receptor-independent activator of G protein signaling, AGS8. J Biol Chem 282:19938-47.
Blumer JB, Kuriyama R, Gettys TW and Lanier SM. (2006) The G-protein regulatory (GPR) motif-containing Leu-Gly-Asn-enriched protein (LGN) and Gialpha3 influence cortical positioning of the mitotic spindle poles at metaphase in symmetrically dividing mammalian cells. Eur J Cell Biol 85:1233-40.
Sato M, Cismowski MJ, Toyota E, Smrcka AV, Lucchesi PA, Chilian WM and Lanier SM. (2006) Identification of a receptor-independent activator of G-protein signaling (AGS8) in ischemic heart and its interaction with G¸ˇ. Proc Natl Acad of Sciences 103:797-802.
Simon V, Guidry J, Gettys TW, Tobin AB and Lanier SM. (2006) The Proto-oncogene SET Interacts with Muscarinic Receptors and Attenuates Receptor Signaling. J Biol Chem 281(52):40310-20.
Books and Monographs
Blumer JB, Smrcka AV and Lanier SM. (2007) “Mechanistic pathways and biological roles for receptor-independent activators of G-protein signaling.” Pharmacology and Therapeutics. Editors David Sibley and Jurgen Wess.
Blumer JB, Sato M and Lanier SM. (2007) AGS3. UCSD-Nature Molecule Pages. Published online: 27 Nov 2007 http://www.signaling-gateway.org/molecule/query?afcsid=A000228
Lanier SM, Struckhoff AP and Cismowski MJ. (2007) AGS1. UCSD-Nature Molecule Pages. Published online: 21 Nov 2007 http://www.signaling-gateway.org/molecule/query?afcsid=A000226
Sato M, Blumer JB, Simon V and Lanier SM. (2006) “Accessory proteins for G proteins: Partners in signaling.” Annual Review of Pharmacology and Toxicology 46:151-87.
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