An RGD sequence in the P2Y2 receptor interacts with αvβ3 integrins and is required for Go-mediated signal transduction
The P2Y nucleotide receptor (P2Y R) contains the integrin-binding domain arginine-glycine-aspartic acid (RGD) in its first èxtracellular loop, raising the possibility that this G protein-coupled receptor interacts directly with an integrin. Binding of a peptide corresponding to the first extracellular loop of the P2Y R to K562 erythroleukemia cells was inhibited by antibodies against α β /β integrins and the integrin-associated thrombospondin receptor, CD47. Immunofluorescence of cells transfected with epitope-tagged P2Y Rs indicated that α integrins colocalized 10-fold better with the wild-type P2Y R than with a mutant P2Y R in which the RGD sequence was replaced with RGE. Compared with the wild-type P2Y R, the RGE mutant required 1,000-fold higher agonist concentrations to phosphorylate focal adhesion kinase, activate extracellular signal-regulated kinases, and initiate the PLC-dependent mobilization of intracellular Ca . Furthermore, an anti-α integrin antibody partially inhibited these signaling events mediated by the wild-type P2Y R. Pertussis toxin, an inhibitor of G proteins, partially inhibited Ca mobilization mediated by the wild-type P2Y R, but not by the RGE mutant, suggesting that the RGD sequence is required for P2Y R-mediated activation of G , but not G . Since CD47 has been shown to associate directly with G , family proteins, these results suggest that interactions between P2Y Rs, integrins, and CD47 may be important for coupling the P2Y R to G . 2 2 2 v 3 5 2 v 2 2 2 v 2 i/o 2 2 o q i/o 2 2 o 2+ 2+
Cell surface receptors, GTP-binding proteins, Integrins, Purinergic receptors, Signal transduction
Reinacher-Schick, Anke, and Barry M. Gumbiner. "Apical membrane localization of the adenomatous polyposis coli tumor suppressor protein and subcellular distribution of the β-catenin destruction complex in polarized epithelial cells." The Journal of cell biology 152, no. 3 (2001): 491-502.
Journal of Cell Biology