The delta subunit of rod specific cyclic GMP phosphodiesterase, PDE δ, interacts with the Arf-like protein Arl3 in a GTP specific manner

Recently, we have shown that the delta subunit of the cGMP phosphodiesterase (PDE delta) interacts with the retinitis pigmentosa guanine regulator (RPGR), Here, using the two-hybrid system, we identify a member of the Arf-like protein family of Ras-related GTP-binding proteins, Arl3, that interacts with PDE delta, The interaction was verified by fluorescence spectroscopy and co-immunoprecipitation. Arl3 features an unusually low affinity for guanine nucleotides, with a K-D of 24 nM for CDP and 48 mu M for GTP. Fluorescence spectroscopy shows that PDE delta binds and specifically stabilizes the GTP-bound form of Arl3 by strongly decreasing the dissociation rate of GTP, Thus, PDE delta is an effector of Arl3 and could provide a novel nucleotide exchange mechanism by which PDE delta stabilizes Arl3 in its active GTP-bound form. (C) 1999 Federation of European Biochemical Societies.