The Arf GAP AGAP2 Interacts with {beta}Arrestin2 and Regulates {beta}2-Adrenergic Receptor Recycling and Erk Activation

AGAP2 is a multidomain Arf GAP (ADP ribosylation factor-directed GTPase-activating protein) that was shown to promote the fast-recycling of transferrin receptors. Here, we tested the hypothesis that AGAP2 regulates trafficking of β2-adrenergic receptors. We found that AGAP2 formed a complex with βArrestin1 and βArrestin2, proteins that are known to regulate β2-adrenergic receptor signaling and trafficking. AGAP2 colocalized with βArrestin2 on the plasma membrane, and knockdown of AGAP2 expression reduced plasma membrane association of βArrestin2 upon β2-adrenergic receptor activation. AGAP2 also colocalized with internalized β2-adrenergic receptors on endosomes, and overexpression of AGAP2 slowed accumulation of β2-adrenergic receptor in the perinuclear recycling endosomes. On the contrary, knockdown of AGAP2 expression prevented recycling of β2-adrenergic receptor back to the plasma membrane. In addition, AGAP2 formed a complex with endogenous Erk and overexpression of AGAP2 potentiated Erk phosphorylation induced by β2-adrenergic receptors. Taken together, these results support the hypothesis that AGAP2 plays a role in the signaling and recycling of β2-adrenergic receptors.

Source: BJ Cell - March 26, 2013 Category: Biochemistry Authors: Y Wu, Y Zhao, X Ma, Y Zhu, J Patel, Z Nie Tags: BJ Cell Source Type: research