The A2A adenosine receptor is a G protein-coupled receptor which desensitizes upon prolonged agonist stimulation. In order to understand the biological function of its unusually long C-terminus, we screened a human brain library for proteins capable of binding to the last 120 amino acids of the A2A receptor. We identified a guanine nucleotide exchange factor for the small G protein ARF6 (ARNO/c...

Epidermal growth factor (EGF) and insulin-like growth factor-I (IGF-I) are critical regulators of cell differentiation, survival, proliferation, and migration in cancers. This study found that ARNO (cytohesin-2), an activator of the EGF and IGF-I pathways, was more highly expressed in colorectal cancer tissue than in benign adjacent colorectal tissue. When ARNO-siRNA or the chemical inhibitor S...

BACKGROUND Recent findings from our laboratory have demonstrated that glucose-stimulated insulin secretion (GSIS) involves interplay between a variety of small G proteins belonging to the Rho (e.g., Cdc42 and Rac1) and ADP-ribosylation factor (e.g., Arf6) subfamilies. Using immunological, pharmacological and molecular biological approaches, we have also identified guanine nucleotide exchange fa...

In the developing nervous system, controlled neurite extension and branching are critical for the establishment of connections between neurons and their targets. Although much is known about the regulation of axonal development, many of the molecular events that regulate axonal extension remain unknown. ADP-ribosylation factor nucleotide-binding site opener (ARNO) and ADP-ribosylation factor (A...

Salmonella virulence effectors elicit host cell membrane ruffling to facilitate pathogen invasion. The WAVE regulatory complex (WRC) governs the underlying membrane-localized actin polymerization, but how Salmonella manipulates WRC is unknown. We show that Rho GTPase activation by the Salmonella guanine nucleotide exchange factor (GEF) SopE efficiently triggered WRC recruitment but not its acti...

In the developing nervous system, controlled neurite extension and branching are critical for the establishment of connections between neurons and their targets. Although much is known about the regulation of axonal development, many of the molecular events that regulate axonal extension remain unknown. ADP-ribosylation factor nucleotidebinding site opener (ARNO) and ADP-ribosylation factor (AR...

The small GTPase ARF1 is a key regulator of intracellular membrane traffic. In its active, GTP-bound form, ARF1 is associated with Golgi membranes and promotes the recruitment of the cytosolic coat protein complex, which will result in membrane budding and vesicle formation. ARNO (ARF nucleotide site opener) has been shown to act in vitro as a GTP exchange factor for ARF1. Here, we have investi...