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.
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.
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.