GPCRs transduce signals through a variety of cascades and elicit diverse biophysical activities. Therapeutic compounds targeting GPCRs (no matter biologics and small molecules) are designed to interfere with GPCR functionalities via activating (agonist) or blocking (antagonist) certain pathways. Hence, to characterize and understand the agonistic/antagonistic potentials against target GPCR is very critical for GPCR drug discovery. In order to address this demand, Creative Biolabs has launched a full portfolio of GPCR stable cell lines engineered with unique biosensor that can specifically link second messenger activation (i.e. Ca2+, cAMP, DAG) to fluorescent changes, which can effectively facilitate compound screening & characterization.
DAG Signaling Pathway
Multiple G-protein isoforms play vital roles in signal transduction, the Gq is a subtype of G-protein alpha subunits and involved in the activation of the phosphatidylinositol signaling pathway. Gq protein can activate phospholipase C (PLC) that cleaves a phosphatidylinositol 4,5-bisphosphate (PIP2) into diacyl glycerol (DAG) and inositol 1,4,5-trisphosphate (IP3). IP3 is released into the cytosol while DAG still bounds to the membrane. IP3 then diffuses through the cytosol to bind to IP3 receptors, especially calcium channels in the endoplasmic reticulum (ER). These channels are specific to calcium and only allow the passage of calcium to move through. This will subsequently lead to an increase of cytosolic concentration of calcium, resulting in a cascade of cellular biophysical activities. DAG pathway plays an important part in a wide variety of human bodily processes. For example, thrombin receptors in platelets rely on this pathway to promote blood clotting.
Fig. 1 General scheme of DAG and PA.1
DAG-activated GPCR Cell Lines
Our Magic™ stable cell lines co-expressing fluorescent biosensors and target GPCRs are specifically developed to test drug compounds that interact with DAG signaling pathway. Cytosol-oriented fluorescence can be observed momentarily in respond to DAG activation. These featured cell lines have been widely used as an innovative and sensitive tool for studying the molecular MOA and kinetics underlying GPCR drug candidates. Currently, we provide a wide range of Magic™ GPCR stable cell lines engineered with DAG-activated biosensor:
With years of non-stop efforts, scientists in Creative Biolabs are happy to leverage our expertise and resources to help our clients and address diverse custom demands. We offer customized work plans tailored to satisfy each specific requirements from our customers. Please contact us for more information and a detailed quote.
Reference
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