title: The Arf GAP AGAP2 interacts with β-arrestin2 and regulates β2-adrenergic receptor recycling and ERK activation.
abstract: AGAP2 [Arf (ADP-ribosylation factor) GAP (GTPase-activating protein) with GTP-binding-protein-like, ankyrin repeat and PH (pleckstrin homology) domains] is a multidomain Arf GAP that was shown to promote the fast recycling of transferrin receptors. In the present study we tested the hypothesis that AGAP2 regulates the trafficking of β2-adrenergic receptors. We found that AGAP2 formed a complex with β-arrestin1 and β-arrestin2, proteins that are known to regulate β2-adrenergic receptor signalling and trafficking. AGAP2 co-localized with β-arrestin2 on the plasma membrane, and knockdown of AGAP2 expression reduced plasma membrane association of β-arrestin2 upon β2-adrenergic receptor activation. AGAP2 also co-localized with internalized β2-adrenergic receptors on endosomes, and overexpression of AGAP2 slowed accumulation of β2-adrenergic receptor in the perinuclear recycling endosomes. In contrast, knockdown of AGAP2 expression prevented the recycling of the β2-adrenergic receptor back to the plasma membrane. In addition, AGAP2 formed a complex with endogenous ERK (extracellular-signal-regulated kinase) 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 signalling and recycling of β2-adrenergic receptors.
authors.affiliation: Department of Urology and Prostate Disease Center, University of Florida College of Medicine, Gainesville, FL 32610, USA.
authors.forename: Yuanjun
authors.initials: Y
authors.lastname: Wu
authors.forename: Yu
authors.initials: Y
authors.lastname: Zhao
authors.forename: Xiaojie
authors.initials: X
authors.lastname: Ma
authors.forename: Yunjuan
authors.initials: Y
authors.lastname: Zhu
authors.forename: Jaimin
authors.initials: J
authors.lastname: Patel
authors.forename: Zhongzhen
authors.initials: Z
authors.lastname: Nie
mesh_terms: D019390:Arrestins / Q000378:metabolism*; D045744:Cell Line, Tumor; D004789:Enzyme Activation / Q000235:genetics; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism*; D019204:GTP-Binding Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism* / Q000502:physiology; D020690:GTPase-Activating Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism* / Q000502:physiology; D055785:Gene Knockdown Techniques; D057809:HEK293 Cells; D006801:Humans; D011485:Protein Binding / Q000235:genetics; D021381:Protein Transport / Q000235:genetics; D018343:Receptors, Adrenergic, beta-2 / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction / Q000235:genetics; D000071557:beta-Arrestins
chemical_list: D019390:Arrestins; D020690:GTPase-Activating Proteins; D018343:Receptors, Adrenergic, beta-2; D000071557:beta-Arrestins; D048049:Extracellular Signal-Regulated MAP Kinases; C485997:AGAP2 protein, human; D019204:GTP-Binding Proteins