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

Abstract

Recently, we have shown that the δ subunit of the cGMP phosphodiesterase (PDE δ) 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 δ. 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 GDP and 48 μM for GTP. Fluorescence spectroscopy shows that PDE δ binds and specifically stabilizes the GTP-bound form of Arl3 by strongly decreasing the dissociation rate of GTP. Thus, PDE δ is an effector of Arl3 and could provide a novel nucleotide exchange mechanism by which PDE δ stabilizes Arl3 in its active GTP-bound form. Copyright (C) 1999 Federation of European Biochemical Societies.