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. Author manuscript; available in PMC: 2009 Jun 8.
Published in final edited form as: FEBS Lett. 2008 Apr 16;582(12):1637–1642. doi: 10.1016/j.febslet.2008.04.009

Figure 1.

Figure 1

Inhibition of ROCK by multiple inhibitors suppresses polyglutamine aggregation. (A-C) Dose-response of pharmacologic inhibitors of ROCK. HEK293 cells were transfected with ARN127(Q65)CFP/YFP and treated with (A) Y-27632, (B) HA-1077, or (C) H-1152P at the indicated concentrations. FRET values representing aggregation were determined on the fluorescence plate reader. The relative drug responses were calculated, with 1 indicating maximal aggregation inhibition. All drugs dose-dependently inhibited polyglutamine aggregation. (D) A C-terminal auto-inhibitory fragment of ROCK 2 containing the RBPH domain was mutated at two sites (N1036T, K1037T) to abolish Rho-binding. (E-F) Pharmacologic and peptide-mediated inhibition of ROCK reduces polyglutamine aggregation to similar extents. HEK293 cells were transfected with ARN127(Q65)CFP/YFP (E) or Htt Exon 1(Q72)CFP/YFP (F) alone or with RBPH(TT), or were treated for 24hr with Y-27632 (50μM), HA-1077 (40μM) or H-1152P (10μM). Effects were expressed as relative FRET/donor ratios vs. untreated cells or cells transfected with an empty vector. All inhibitors reduced aggregation by 25-30%. Error bars represent the S.E.M.