Receptor heterodimerization: a new level of cross-talk
Peter J. Barnes
Peter J. Barnes
Published May 1, 2006
Citation Information: J Clin Invest. 2006;116(5):1210-1212. https://doi.org/10.1172/JCI28535.
View: Text | PDF
Commentary

Receptor heterodimerization: a new level of cross-talk

Abstract

Most G protein–coupled receptors (GPCRs) probably exist as homodimers, but it is increasingly recognized that GPCRs may also dimerize with other types of GPCRs and that this physical interaction may affect the function of either receptor. A study in this issue of the JCI demonstrates how heterodimerization between prostaglandin E receptors and β2–adrenergic receptors (β2ARs) in airway smooth muscle cells results in uncoupling of β2ARs and a diminished bronchodilator response to β2AR agonists (see the related article beginning on page 1400). This illustrates what we believe to be a novel mechanism of receptor cross-talk and highlights the potential importance of GPCR heterodimerization in diseases such as asthma and how this could lead to the development of more specific therapies in the future.

Authors

Peter J. Barnes

×

Figure 1

Heterodimerization of EP1 R and β2 AR in airway smooth muscle cells.

Options: View larger image (or click on image) Download as PowerPoint
Heterodimerization of EP1 R and β2 ...
(A) Under basal conditions, a β2 agonist activates a stimulatory G protein (Gs), thus stimulating adenylyl cyclase (AC) to increase cAMP production and produce bronchodilatation. (B) PGE2 promotes the dimerization of EP1R with β2AR, uncoupling β2AR from Gs, thus reducing the bronchodilator response to a β2AR agonist. EP1R signals through a different G protein (Gq) coupled to phospholipase C (PLC) and the formation of inositol-1,4,5-trisphosphate (IP3), which releases calcium ions to cause bronchoconstriction, but PGE2 alone does not activate this pathway sufficiently to induce bronchoconstriction. PIP2, phosphatidylinositol-4,5-biphosphate.