scholarly journals Modulating G-Protein Coupled Receptor/G-Protein Signal Transduction by Small Molecules Suggested by Virtual Screening

2008 ◽  
Vol 51 (17) ◽  
pp. 5297-5303 ◽  
Author(s):  
Christina M. Taylor ◽  
Yaniv Barda ◽  
Oleg G. Kisselev ◽  
Garland R. Marshall
Keyword(s):  
Signal Transduction ◽  
Virtual Screening ◽  
Small Molecules ◽  
G Protein ◽  
G Protein Coupled Receptor ◽  
G Protein Coupled

scholarly journals Smoothened Signal Transduction Is Promoted by G Protein-Coupled Receptor Kinase 2

2006 ◽  
Vol 26 (20) ◽  
pp. 7550-7560 ◽  
Author(s):  
Alison R. Meloni ◽  
Gregory B. Fralish ◽  
Patrick Kelly ◽  
Ali Salahpour ◽  
James K. Chen ◽  
...  
Keyword(s):  
Signal Transduction ◽  
G Protein ◽  
Sonic Hedgehog ◽  
Cellular Proliferation ◽  
Receptor Kinase ◽  
G Protein Coupled Receptor ◽  
Positive Role ◽  
Proliferation And Differentiation ◽  
Hedgehog Proteins ◽  
G Protein Coupled

ABSTRACT Deregulation of the Sonic hedgehog pathway has been implicated in an increasing number of human cancers. In this pathway, the seven-transmembrane (7TM) signaling protein Smoothened regulates cellular proliferation and differentiation through activation of the transcription factor Gli. The activity of mammalian Smoothened is controlled by three different hedgehog proteins, Indian, Desert, and Sonic hedgehog, through their interaction with the Smoothened inhibitor Patched. However, the mechanisms of signal transduction from Smoothened are poorly understood. We show that a kinase which regulates signaling by many “conventional” 7TM G-protein-coupled receptors, G protein-coupled receptor kinase 2 (GRK2), participates in Smoothened signaling. Expression of GRK2, but not catalytically inactive GRK2, synergizes with active Smoothened to mediate Gli-dependent transcription. Moreover, knockdown of endogenous GRK2 by short hairpin RNA (shRNA) significantly reduces signaling in response to the Smoothened agonist SAG and also inhibits signaling induced by an oncogenic Smoothened mutant, Smo M2. We find that GRK2 promotes the association between active Smoothened and β-arrestin 2. Indeed, Gli-dependent signaling, mediated by coexpression of Smoothened and GRK2, is diminished by β-arrestin 2 knockdown with shRNA. Together, these data suggest that GRK2 plays a positive role in Smoothened signaling, at least in part, through the promotion of an association between β-arrestin 2 and Smoothened.

scholarly journals Residues in the First Extracellular Loop of a G Protein-coupled Receptor Play a Role in Signal Transduction

2002 ◽  
Vol 277 (34) ◽  
pp. 30581-30590 ◽  
Author(s):  
Ayça Akal-Strader ◽  
Sanjay Khare ◽  
Dong Xu ◽  
Fred Naider ◽  
Jeffrey M. Becker
Keyword(s):  
Signal Transduction ◽  
G Protein ◽  
Extracellular Loop ◽  
G Protein Coupled Receptor ◽  
G Protein Coupled

scholarly journals Ric-8A potentiates Gq-mediated signal transduction by acting downstream of G protein-coupled receptor in intact cells

2006 ◽  
Vol 11 (5) ◽  
pp. 487-498 ◽  
Author(s):  
Akiyuki Nishimura ◽  
Miyuki Okamoto ◽  
Yo Sugawara ◽  
Norikazu Mizuno ◽  
Junji Yamauchi ◽  
...  
Keyword(s):  
Signal Transduction ◽  
G Protein ◽  
G Protein Coupled Receptor ◽  
Intact Cells ◽  
G Protein Coupled
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