title: Beta-2 adrenergic receptor mediated ERK activation is regulated by interaction with MAGI-3.
abstract: The beta-2 adrenergic receptor (beta2AR) has a carboxyl terminus motif that can interact with PSD-95/discs-large/ZO1 homology (PDZ) domain-containing proteins. In this paper, we identified membrane-associated guanylate kinase inverted-3 (MAGI-3) as a novel binding partner of beta2AR. The carboxyl terminus of beta2AR binds with high affinity to the fifth PDZ domain of MAGI-3, with the last four amino acids (D-S-L-L) of the receptor being the key determinants of the interaction. In cells, the association of full-length beta2AR with MAGI-3 occurs constitutively and is enhanced by agonist stimulation of the receptor. Our data also demonstrated that beta2AR-stimulated extracellular signal-regulated kinase-1/2 (ERK1/2) activation was substantially retarded by MAGI-3 expression. These data suggest that MAGI-3 regulates beta2AR-mediated ERK activation through the physical interaction between beta2AR and MAGI-3.
authors.affiliation: Department of Biochemistry and Molecular Biology, Capital Medical University, Beijing, PR China.
authors.forename: Xiaomei
authors.initials: X
authors.lastname: Yang
authors.forename: Junfang
authors.initials: J
authors.lastname: Zheng
authors.forename: Ying
authors.initials: Y
authors.lastname: Xiong
authors.forename: Hui
authors.initials: H
authors.lastname: Shen
authors.forename: Licui
authors.initials: L
authors.lastname: Sun
authors.forename: Yan
authors.initials: Y
authors.lastname: Huang
authors.forename: Chaoyuan
authors.initials: C
authors.lastname: Sun
authors.forename: Yang
authors.initials: Y
authors.lastname: Li
authors.forename: Junqi
authors.initials: J
authors.lastname: He
mesh_terms: D020816:Amino Acid Motifs / Q000235:genetics; D002352:Carrier Proteins / Q000378:metabolism; D006801:Humans; D008565:Membrane Proteins / Q000378:metabolism*; D019950:Mitogen-Activated Protein Kinase 1 / Q000378:metabolism*; D048052:Mitogen-Activated Protein Kinase 3 / Q000378:metabolism*; D017434:Protein Structure, Tertiary / Q000235:genetics; D011506:Proteins / Q000378:metabolism*; D018343:Receptors, Adrenergic, beta-2 / Q000378:metabolism*
chemical_list: D002352:Carrier Proteins; C496469:MAGI3 protein, human; D008565:Membrane Proteins; D011506:Proteins; D018343:Receptors, Adrenergic, beta-2; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3