Beta-2 adrenergic receptor mediated ERK activation is regulated by interaction with MAGI-3

FEBS Lett. 2010 Jun 3;584(11):2207-12. doi: 10.1016/j.febslet.2010.03.039. Epub 2010 Mar 29.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Motifs / genetics
  • Carrier Proteins / metabolism
  • Humans
  • Membrane Proteins / metabolism*
  • Mitogen-Activated Protein Kinase 1 / metabolism*
  • Mitogen-Activated Protein Kinase 3 / metabolism*
  • Protein Structure, Tertiary / genetics
  • Proteins / metabolism*
  • Receptors, Adrenergic, beta-2 / metabolism*


  • Carrier Proteins
  • MAGI3 protein, human
  • Membrane Proteins
  • Proteins
  • Receptors, Adrenergic, beta-2
  • Mitogen-Activated Protein Kinase 1
  • Mitogen-Activated Protein Kinase 3