Beta-2 adrenergic receptor mediated ERK activation is regulated by interaction with MAGI-3.
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.
Yang
Xiaomei
X
Department of Biochemistry and Molecular Biology, Capital Medical University, Beijing, PR China.
Zheng
Junfang
J
Xiong
Ying
Y
Shen
Hui
H
Sun
Licui
L
Huang
Yan
Y
Sun
Chaoyuan
C
Li
Yang
Y
He
Junqi
J
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*
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