Words similar to cur
Example sentences for: cur
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Using Smo act- and Smo wt-containing membranes, we then performed competition binding studies by adding increasing concentrations of unlabeled Hh-Ag 1.5, KAAD-cyclopamine or Cur61414 in the presence of [ 3H]-Hh-Ag 1.5 (0.
These include: a Hh-protein-blocking antibody, 5E1 [ 23 ] ; a natural product derivative, cyclopamine [ 9 10 ] that has recently been shown to act downstream of Ptc, perhaps at the level of Smo [ 11 ] ; a recently identified synthetic small-molecule inhibitor, Cur61414, which has inhibitory properties similar to cyclopamine [ 17 ] ; and forskolin, an adenylate cyclase/protein kinase A activator that is thought to block Hh signaling by stimulating degradation of members of the Gli family of transcriptional activators [ 2 ] .
The two Hh-signaling antagonists, KAAD-cyclopamine and Cur61414, have shown decreased potency on Smo act-expressing cells, leading to the speculation that they may bind this mutant form of Smo less well than the wild-type form [ 11 17 ] . We sought to determine whether the Hh agonist binds Smo actwith a higher affinity, an observation seen with certain ligands and constitutively active mutants of GPCRs [ 29 ] . To perform this experiment, we isolated membranes from cells transfected with a cDNA construct encoding a tryptophan-to-leucine mutation at residue 539 (W539L) of murine Smo.
In contrast, the competition experiments with cyclopamine (Figure 4d) and Cur61414 (Figure 4e) showed that Hh protein and the agonist differ in their sensitivity to these antagonists.
The Hh-blocking antibody 5E1 had no effect on pathway activation by the agonist (Figure 4b), while forskolin (Figure 4c), cyclopamine (Figure 4d) and Cur61414 (Figure 4e), were all inhibitory.
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