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.
Recent Publications:
Yohe, M.E., Rossman, K.L., Gardner, O.S., Karnoub, A.E., Snyder, J.T., Gershburg, S., Graves, L.M., Der, C.J. and Sondek, J. (2007) Auto-inhibition of the Dbl Family Protein Tim by an N-terminal Helical Motif. J Biol Chem 282(18):13813-13823. Abstract
Chhatriwala, M.K., Betts, L., Worthylake, D.K. and Sondek, J. (2007) The DH and PH Domains of Trio Coordinately Engage Rho GTPases for their Efficient Activation. J Mol Biol 368(5): 1307-1320. Abstract
Jezyk, M.R., Snyder, J.T., Gershberg, S., Worthylake, D.K., Harden, T.K. and Sondek, J. (2006). Crystal structure of Rac1 bound to its effector phospholipase C-β2. Nat Struct Mol Biol 13(12): 1135-40. Abstract
Harden TK, Sondek J. (2006) Regulation of phospholipase C isozymes by ras superfamily GTPases. Annu Rev Pharmacol Toxicol 46: 355-79. Abstract
Zhou, Y., Wing, M.R., Sondek, J., and Harden, T.K. (2005) Molecular cloning and characterization of PLC-η2.
Biochem J 2391(Pt.3): 667-76. Abstract
Rossman, K.L., Der, C.J. and Sondek, J. (2005) GEF means GO: Turning on Rho GTPase with guanine nucleotide exchange factors. Nat Rev Mol Cell Biol 6(4): 167-180. Abstract
