John Sondek, PhD



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.


    • 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.
    • 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.
    • 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.
    • 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.
    • 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.
    • 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.


      4060 Genetic Medicine
      Campus Box # 7365
      Chapel Hill, NC 27599

      Office: 919-966-7530
      Lab: 919-966-4628
      Fax: 919-966-5640

      Sondek Lab Website