Inhibitors of phosphoinositide 3-kinase cause defects in the postendocytic sorting of beta2-adrenergic receptors.

Phosphatidylinositol 3-kinase inhibitors have been shown to affect endocytosis or subsequent intracellular sorting in various receptor systems. Agonist-activated beta(2)-adrenergic receptors undergo desensitization by mechanisms that include the phosphorylation, endocytosis and degradation of receptors. Following endocytosis, most internalized receptors are sorted to the cell surface, but some proportion is sorted to lysosomes for degradation.

Endosome sorting of beta 2-adrenoceptors is GRK5 independent.

1. We have investigated the role of G protein-coupled receptor kinase 5 (GRK5) in the regulation of endosome sorting of human beta(2)-adrenoceptors. 2.

Regulation of G-protein-coupled receptor activity by rab GTPases.

The regulation of G-protein-coupled receptor (GPCR) activity involves a diversity of vesicular transport processes. Receptor desensitization and resensitization are intimately connected with membrane trafficking events such as endocytosis, intracellular sorting, transport to lysosomes, and recycling to the plasma membrane. Ras-related GTPases of the rab family are known to regulate these processes, including a subset of rab proteins that are specific for endosomes and lysosomes.