The GoLoco motif - structural and cell biological analyses of novel guanine nucleotide dissociation inhibitors for G-alpha subunits
Characterization of the signaling scaffold activities of RGS12 and RGS14 in coordinating heterotrimeric G-protein, Ras-superfamily GTPase, and receptor tyrosine kinase signal transduction pathways
Research Synopsis:
"Regulator of G-protein signaling" (RGS) proteins are modular, multi-domain proteins
that accelerate the GTPase activity of G-protein alpha subunits. The Siderovski lab first
recognized these critical regulators of signal transduction timing in 1996. The laboratory
continues to study their structural and functional diversity, their new-found appreciation as
more than mere attenuators of signaling, and their specific roles in (patho)physiological
processes.
Recent Publications:
Willard, M.D., Willard, F.S., Li, X., Cappell, S.D., Snider, W.D., and Siderovski, D.P. (2007) Selective role for RGS12 as a Ras/Raf/MEK scaffold in nerve growth factor-mediated differentiation. EMBO Journal 26: 2029-2040. Abstract
Johnston, C.A., and Siderovski, D.P. (2007) Structural basis for nucleotide exchange on G alpha i subunits and receptor coupling specificity. Proc Natl Acad Sci USA 104: 2001-2006. Abstract
Liu, H., Suresh, A., Willard, F.S., Siderovski, D.P., Lu, S., Naqvi, N.I. (2007) Rgs1 regulates multiple Galpha subunits in Magnaporthe pathogenesis, asexual growth and thigmotropism. EMBO Journal 26: 690-700. Abstract
Afshar K, Willard FS, Colombo K, Johnston CA, McCudden CR, Siderovski DP,
Gonczy P.
(2004) RIC-8 is required for GPR-1/2-dependent Galpha function during asymmetric
division of C. elegans embryos.
Cell 119: 219-30. Abstract
Chen JG, Willard FS, Huang J, Liang J, Chasse SA, Jones AM, Siderovski DP.
(2003) A seven-transmembrane RGS protein that modulates plant cell proliferation.
Science 301: 1728-31. Abstract
Colombo K, Grill SW, Kimple RJ, Willard FS, Siderovski DP, Gonczy P.
(2003) Translation of polarity cues into asymmetric spindle positioning in
Caenorhabditis elegans embryos. Science 300: 1957-61. Abstract
Kimple RJ, Kimple ME, Betts L, Sondek J, Siderovski DP. (2002)
Structural determinants for GoLoco-induced inhibition of nucleotide
release by
Galpha subunits.
Nature 416: 878-81. Abstract
