G protein signaling constitutes a fundamental mechanism of intercellular communication used by all eukaryotes. The signaling pathways have several components, each encoded by distinct multigene families. G proteins couple extracellular signals received by receptors to the regulation of effector proteins that generate intracellular second messengers. Recently, a new family of proteins was identified, termed the Regulators of G protein Signaling (RGS). Genetic evidence suggested RGS proteins inhibited G protein signaling. Subsequent biochemical analysis demonstrated RGS proteins were GTPase activating proteins (GAPs) in vitro, consistent with their in vivo function as inhibitors of G protein signaling. Mammals utilize these elaborate mechanisms to initiate and terminate G protein signaling in sensory transduction systems and a variety of other specialized functions in terminally differentiated cells. G proteins are also expressed early in mammalian development and in pluripotent progenitor cells of adults, but little is known about their biological functions in these settings. Our laboratory is using transgenic and mouse embryonic stem (ES) cell technology, in conjunction with biochemical studies, to address the role of G protein signaling in mammalian development and adult physiology and behavior.
RESEARCH INTERESTS
G Protein Signaling in Mammalian Development, Adult Physiology and Behavior
RECENT PUBLICATIONS
Huang J, Pashkov V, Kurrasch DM, Yu K, Gold SJ, & Wilkie TM., "Feeding and fasting controls liver expression of a Regulator of G protein Signaling (Rgs16) in periportal hepatocytes." Comparative Hepatology, 5:doi:10.1186/1476-5926-5-8, 2006
Wilkie TM & Kinch L., "New roles for Ga and RGS proteins: Communication continues despite driving sisters apart." Current Biology, 15:R843-R854, November 2005
Sierra DA, Gilbert DJ, Householder D, Grishin NV, Yu K, Ukidwe P, Barker S, He W, Wensel TG, Otero G, Brown G, Copeland NG, Jenkins NA & Wilkie TM, "Evolution of the regulators of G protein signaling (RGS) multigene family in mouse and human." Genomics, 79:177-185, 2002
Ivey K, Tyson B, Ukidwe P, McFadden D, Levi G, Olson E, Srivastava D & Wilkie TM, "G alpha-q and Galpha-11 proteins mediate endothelin-1 signaling in neural crest-derived pharyngeal arch mesenchyme." Developmental Biology, 255:230-237, 2003
Luo X, Popov S, Bera AK, Wilkie TM & Muallem S, "Regulators of G protein signaling provide biochemical control of agonist-evoked [Ca2+]i oscillations." Molecular Cell, 7:651-660, 2001
SIGNIFICANT PUBLICATIONS
Ross EM & Wilkie TM, "GTPase-activating proteins (GAPs) for heterotrimeric G proteins: Regulators of G protein signaling (RGS proteins) and their relatives." Annual Review of Biochemistry, 69:795-827, 2000
Popov S, Krishna UM, Falck JR & Wilkie TM, "Ca2+/calmodulin reverses 3,4,5-trisphosphate-dependent inhibition of regulators of G protein-signaling GTPase-activating protein activity." J. Biol. Chem., 275:18962-18968, 2000
Zeng W, Xu X, Popov S, Mukhopadhyay S, Chidiac P, Swistok J, Danho W, Yagaloff K, Fisher S, Ross EM, Muallem S & Wilkie TM, "The N-terminal domain of RGS4 confers receptor selective inhibition of G protein signaling" J. Biol. Chem., 273:34687-34690, 1998
Popov S, Yu K, Kozasa T & Wilkie TM, "The RGS domains of RGS4, RGS10 and GAIP retain GAP activity in vitro." Proc. Natl. Acad Sci. USA, 94:7216-7220, 1997
Berman DM, Wilkie TM & Gilman AG, "GAIP and RGS4 are GTPase accelerating proteins (GAPs) for the Gi family of heterotrimeric guanine nucleotide binding proteins." Cell, 86:445-452, 1996
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