Sphingosylphosphorylcholine (SPC) and lysophosphatidylcholine (LPC) are bioactive lipid molecules involved in numerous biologicals processes. GPR4 shares sequence homology with OGR1 (51%), the highest of all GPCRÕs. GPR4 has been identified as another high affinity receptor for SPC and low affinity receptor for LPC. SPC and LPC stimulate kinase activation and DNA synthesis stimulated, both of which are pertussis toxin-sensitive, suggesting Gi-heterotrimeric G protein involvement. The GPR4 subfamily of GPCRÕs consists of four receptors that share significant sequence homology; OGR1, TDAG8 and G2A. G2A has been shown to be a potent transforming oncogene. GPR4 also malignantly transforms NIH3T3 cells and TDAG8 malignantly transforms the normal mammary epithelial cell line NMuMG. Overexpression of GPR4 or TDGA8 in HEK293 cells leads to transcriptional activation independent of exogenously added ligand. TDAG8 and GPR4 are also overexpressed in a range of human cancer tissues suggestive of a driving role in maintaining tumor formation.
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