Rab11 regulates the recycling of the beta2-adrenergic receptor through a direct interaction.

The beta2ARs (beta(2)-adrenergic receptors) undergo ligand-induced internalization into early endosomes, but then are rapidly and efficiently recycled back to the plasma membrane, restoring the numbers of functional cell-surface receptors. Gathering evidence suggests that, during prolonged exposure to agonist, some beta2ARs also utilize a slow recycling pathway through the perinuclear recycling endosomal compartment regulated by the small GTPase Rab11. In the present study, we demonstrate by co-immunoprecipitation studies that there is a beta2AR-Rab11 association in HEK-293 cells (human embryonic kidney cells).

RACK1 regulates the cell surface expression of the G protein-coupled receptor for thromboxane A(2).

We used the yeast two-hybrid system to screen for proteins that interact with the C-terminus of the beta isoform of the thromboxane A(2) receptor (TPbeta). This screen identified receptor for activated C-kinase 1 (RACK1) as a new TPbeta-interacting protein. Here, we show that RACK1 directly binds to the C-terminus and the first intracellular loop of TPbeta.

Peroxiredoxin-4 interacts with and regulates the thromboxane A(2) receptor.

We identified peroxiredoxin-4 (Prx-4) as a protein interacting with the beta isoform of the thromboxane A(2) receptor (TPbeta) by yeast two-hybrid analysis. Prx-4 co-immunoprecipitated constitutively with TPbeta in HEK293 cells. The second and third intracellular loops as well as the C-terminus of TPbeta interacted directly with Prx-4.

Differential regulation of the signaling and trafficking of the two prostaglandin D2 receptors, prostanoid DP receptor and CRTH2.

Prostaglandin D2 (PGD2) exerts its actions on two G protein-coupled receptors, the prostanoid DP receptor and CRTH2 (chemoattractant homologous receptor expressed on TH2 cells). Here, we characterize the regulation of the signaling and trafficking of the prostanoid DP receptor and CRTH2. Time-course and dose-response curves showed that both receptors expressed in HEK293 cells internalized maximally after 2 h of stimulation with 1 microM PGD2.

The intracellular trafficking of the G protein-coupled receptor TPbeta depends on a direct interaction with Rab11.

Intracellular trafficking pathways of cell surface receptors following their internalization are the subject of intense research efforts. However, the mechanisms by which they recycle back to the cell surface are still poorly defined. We have recently demonstrated that the small Rab11 GTPase protein is a determinant factor in controlling the recycling to the cell surface of the beta-isoform of the thromboxane A2 receptor (TPbeta) following its internalization.

Nm23-H2 interacts with a G protein-coupled receptor to regulate its endocytosis through an Rac1-dependent mechanism.

G protein-coupled receptors (GPCRs) represent a vast family of transmembrane proteins involved in the regulation of several physiological responses. The thromboxane A2 receptor (present as two isoforms: TP alpha and TP beta) is a GPCR displaying diverse pharmacological effects. As seen for many other GPCRs, TP beta is regulated by agonist-induced internalization.