Extended Human G‑Protein Coupled Receptor Network: Cell-Type-Specific Analysis of G‑Protein Coupled Receptor Signaling Pathways

G-protein coupled receptors (GPCRs) mediate crucial physiological
functions in humans, have been implicated in an array of diseases,
and are therefore prime drug targets. GPCRs signal via a multitude
of pathways, mainly through G-proteins and β-arrestins, to regulate
effectors responsible for cellular responses. The limited number of
transducers results in different GPCRs exerting control on the same
pathway, while the availability of signaling proteins in a cell defines
the result of GPCR activation. The aim of this study was to construct
the extended human GPCR network (hGPCRnet) and examine the effect
that cell-type specificity has on GPCR signaling pathways. To achieve
this, protein–protein interaction data between GPCRs, G-protein
coupled receptor kinases (GRKs), Gα subunits, β-arrestins,
and effectors were combined with protein expression data in cell types.
This resulted in the hGPCRnet, a very large interconnected network,
and similar cell-type-specific networks in which, distinct GPCR signaling
pathways were formed. Finally, a user friendly web application, hGPCRnet
(http://bioinformatics.biol.uoa.gr/hGPCRnet), was created to allow for the visualization and exploration of
these networks and of GPCR signaling pathways. This work, and the
resulting application, can be useful in further studies of GPCR function
and pharmacology.