Research article

Heterodimerization of β₂ adrenergic receptor and somatostatin receptor 5: Implications in modulation of signaling pathway

Rishi K Somvanshi, Nicole Chaudhari, Xiaofan Qiu and Ujendra Kumar^*

• * Corresponding author: Ujendra Kumar ujkumar@mail.ubc.ca

Author Affiliations

Faculty of Pharmaceutical Sciences, The University of British Columbia, Vancouver, BC, Canada

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Journal of Molecular Signaling 2011, 6:9 doi:10.1186/1750-2187-6-9

Published: 12 August 2011

Abstract

Background

In the present study, we describe heterodimerization between human-Somatostatin Receptor 5 (hSSTR5) and β₂-Adrenergic Receptor (β₂AR) and its impact on the receptor trafficking, coupling to adenylyl cyclase and signaling including mitogen activated protein kinases and calcineurin-NFAT pathways.

Methods

We used co-immunoprecipitation, photobleaching- fluorescence resonance energy transfer and Fluorescence assisted cell sorting analysis to characterize heterodimerization between SSTR5 and β₂AR.

Results

Our results indicate that hSSTR5/β₂AR exist as preformed heterodimers in the basal condition which is enhanced upon co-activation of both receptors. In contrast, the activation of individual receptors leads to the dissociation of heterodimers. Receptor coupling to adenylyl cyclase displayed predominant effect of β₂AR, however, somatostatin mediated inhibition of cAMP was enhanced upon blocking β₂AR. Our results indicate hSSTR5 mediated significant activation of ERK1/2 and inhibition of phospho-p38. The phospho-NFAT level was enhanced in cotransfected cells indicating the blockade of calcineurin mediated dephosphorylation of NFAT upon receptor heterodimerization.

Conclusion

These data for the first time unveil a novel insight for the role of hSSTR5/β₂AR in the modulation of signaling pathways which has not been addressed earlier.