Figure 6.

Dominant-negative activity of the novel CRFR1 splice variant j on the full-length CRFR1α receptor. A, Activation of a cAMP-response element luciferase reporter by sauvagine (0.1 nM, 1 nM) in HEK293T cells transfected with a fixed amount of CRFR1α and increasing amounts of CRFR1j. Luciferase activity decreased with increasing CRFR1j at both concentrations of sauvagine (P < .001 for both analyses), indicating a potential dominant-negative effect of CRFR1j on CRFR1 signaling. B, Cell surface expression of CRFR1α in COSM6 cells transfected with myc-tagged CRFR1α alone or in combination with CRFR1j, showing reduced cell surface expression in cotransfected cells. Experiments were performed in triplicate. Data represent means and SEs. Statistics compare sauvagine treatment with the no-treatment group for each transfection, unless otherwise indicated. *, P < .05, **, P < .01, ***, P < .001 (ns, P > .05).