Department of Pharmacology
- Rho GTPases
- heterotrimeric G proteins
- phospholipase C isozymes
- avirulence factors
- drug discovery
- new methods for protein production
Our laboratory studies signal transduction systems controlled by heterotrimeric G proteins as well as Ras-related GTPases. The superfamily of GTPases control numerous signaling cascades based upon the regulated binding, hydrolysis, and exchange of guanine nucleotides; GTPases bound to GTP are active in downstream signaling while those bound to GDP are inactive. Mutant GTPases with abnormal GDP/GTP cycling are implicated in numerous human diseases, including cancer. It is our desire to better understand the regulation of heterotrimeric G proteins and Ras-related GTPases at the molecular level with the ultimate goal of using this information to design therapies to correct abnormal signaling mediated by these proteins and thereby treat associated pathologies.
Click above for PubMed publications.
- Waldo, G.L., Ricks, T.K., Hicks, S.N., Cheever, M.L., Kawano, T., Tzuboi, K., Wang, X., Montell, C., Kozasa, T., Sondek, J. and Harden, T.K. (2010) Kinetic Scaffolding Mediated by a Phospholipase C-β and Gq Signaling Complex. Science 330: 974-980. Abstract
- Gresset A, Hicks SN, Harden TK and Sondek J. (2010) Mechanism of Phosphorylation-induced Activation of Phospholipase C-g Isozymes. J Biol Chem. 285(46):35836-35847. Abstract
- Hicks, S.N., Jezyk, M.R., Gershburg, S., Seifert, J.P., Harden, T.K. and Sondek, J. (2008). General and versatile autoinhibition of PLC isozymes. Mol. Cell 31, 383-394. Abstract
- Cheever, M.L, Snyder, J.T., Gershburg, S., Siderovski, D.P., Harden, T.K. and Sondek, J. (2008). Crystal structure of the multifunctional Gb5-RGS9 complex. Nat. Struct. Mol. Biol. 15, 155 – 162. Abstract
- Yohe ME, Rossman K and Sondek J. (2008) Role of the C-terminal SH3 domain and N-terminal tyrosine phosphorylation in regulation of Tim and related Dbl-family proteins. Biochemistry. 47(26):6827-6839. Abstract
- Rojas, R. J., Yohe, M. E., Gershburg, S., Kawano, T., Kozasa, T. and Sondek, J. (2007). Gαq directly activates p63RhoGEF and Trio via a conserved extension of the DH-associated PH domain. J Biol. Chem. 282, 29201-29210. Abstract