The β2-adrenergic receptor interacts with the Na+/H+-exchanger regulatory factor to control Na+/H+ exchange

@article{Hall1998TheR,
  title={The $\beta$2-adrenergic receptor interacts with the Na+/H+-exchanger regulatory factor to control Na+/H+ exchange},
  author={Randy A. Hall and Richard T. Premont and Chung Wai Chow and Jeremy T. Blitzer and Julie A. Pitcher and Audrey Claing and Robert H. Stoffel and Larry S. Barak and Shirish Shenolikar and Edward J. Weinman and Sergio Grinstein and Robert J. Lefkowitz},
  journal={Nature},
  year={1998},
  volume={392},
  pages={626-630}
}
Stimulation of β2-adrenergic receptors on the cell surface by adrenaline or noradrenaline leads to alterations in the metabolism, excitability, differentiation and growth of many cell types. These effects have traditionally been thought to be mediated exclusively by receptor activation of intracellular G proteins. However, certain physiological effects of β2-adrenergic receptor stimulation, notably the regulation of cellular pH by modulation of Na+/H+ exchanger (NHE) function, do not seem to be… 

A C-terminal motif found in the beta2-adrenergic receptor, P2Y1 receptor and cystic fibrosis transmembrane conductance regulator determines binding to the Na+/H+ exchanger regulatory factor family of PDZ proteins.

The Na+/H+ exchanger regulatory factor (NHERF) binds to the tail of the beta2-adrenergic receptor and plays a role in adrenergic regulation of Na-H+ exchange and may be multifunctional adaptor proteins involved in many previously unsuspected aspects of intracellular signaling.

Stimulation of β2-Adrenergic Receptor Increases Cystic Fibrosis Transmembrane Conductance Regulator Expression in Human Airway Epithelial Cells through a cAMP/Protein Kinase A-independent Pathway*

It is demonstrated by immunohistochemistry that CFTR, β2AR, and EBP50 localize to the apical membrane of HAEC, andalyses of anti-EBP50 protein immunoprecipitate showed that salmeterol induced an increase in the amount of CFTR that binds to EBP 50.

Structural Determinants of the Na+/H+Exchanger Regulatory Factor Interaction with the β2Adrenergic and Platelet-derived Growth Factor Receptors*

Structural insights are provided into the mechanisms by which different side chains at the position −1 of peptide ligands interact with PDZ domains and contribute to the affinity of the PDZ-ligand interaction.

GIPC Interacts with the β1-Adrenergic Receptor and Regulates β1-Adrenergic Receptor-mediated ERK Activation*

GIPC can regulate β1-adrenergic receptor-stimulated, Gi-mediated, ERK activation while having no effect on receptor internalization or Gs-mediated cAMP signaling, according to a yeast two-hybrid screen of a human heart cDNA library.

Concerted Roles of SGK1 and the Na+/H+ Exchanger Regulatory Factor 2 (NHERF2) in Regulation of NHE3

  • C. Yun
  • Biology, Medicine
    Cellular Physiology and Biochemistry
  • 2003
The association ofSGK1 with NHERF2 is necessary for stimulation of NHE3 activity by glucocorticoids, and SGK1 together with N HERF2 stimulates the K+ channel ROMK1, suggesting a broader role of SGK 1 in regulation of ion transport.

Novel β2-adrenergic receptor signaling pathways

A review of various interactions of the β 2 -adrenergic receptor with particular emphasis on their role in regulating β 2 AR signaling and trafficking is discussed.

Direct Binding of the β1 Adrenergic Receptor to the Cyclic AMP-Dependent Guanine Nucleotide Exchange Factor CNrasGEF Leads to Ras Activation

The present study provides the first demonstration of direct physical association between a Ras activator and a GPCR, leading to agonist-induced Ras activation.

A macromolecular complex of β2 adrenergic receptor, CFTR, and ezrin/radixin/moesin-binding phosphoprotein 50 is regulated by PKA

  • A. NarenB. Cobb J. Clancy
  • Biology
    Proceedings of the National Academy of Sciences of the United States of America
  • 2002
It is shown that β2 is the major adrenergic receptor isoform expressed in airway epithelia and that it colocalizes with CFTR at the apical membrane and Deleting the regulatory domain of CFTR abolishes PKA regulation of complex assembly.

Beta-adrenergic receptors in the failing heart: the good, the bad, and the unknown.

  • S. Liggett
  • Biology
    The Journal of clinical investigation
  • 2001
Results indicate that although β1AR and β2AR each couple to Gs, these receptor subtypes must engage distinct signaling pathways, and that cAMP alone may not be the only second messenger that is necessary for adrenergic mediated toxic effects.
...

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