P2Y2 and TrkA receptors interact with Src family kinase for neuronal differentiation.
The crosstalk between the P2Y(2) G-protein-coupled receptor (GPCR) with TrkA receptor tyrosine kinase (RTK) is an important mechanism that regulates neuronal differentiation. We show that Src family kinases (SFK) regulate P2Y(2)-TrkA molecular crosstalk. SFK inhibitors block ATPgammaS/P2Y(2)-promoted enhancement of NGF/TrkA signaling and neuronal differentiation in PC12 cells, abrogate the enhancement by ATPgammaS of neurite outgrowth in primary cultures of dorsal root ganglion neurons, and block co-immunoprecipitation of TrkA, P2Y(2) receptors and SFK. These results identify SFK as mediating nucleotide-enhanced neurotrophin-dependent neuronal differentiation and thus, as a key convergence point for interaction between RTKs and GPCRs.
Arthur
David B
DB
Department of Pharmacology, University of California, San Diego, La Jolla, 92093, USA.
Akassoglou
Katerina
K
Insel
Paul A
PA
D000255:Adenosine Triphosphate / Q000031:analogs & derivatives / Q000494:pharmacology; D000818:Animals; D002454:Cell Differentiation / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D004789:Enzyme Activation / Q000187:drug effects; D047468:Immunoprecipitation; D051379:Mice; D008810:Mice, Inbred C57BL; D020932:Nerve Growth Factor / Q000494:pharmacology; D009474:Neurons / Q000166:cytology* / Q000378:metabolism*; D011485:Protein Binding; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D034741:RNA, Small Interfering / Q000235:genetics; D051381:Rats; D020917:Receptor, trkA / Q000378:metabolism*; D018048:Receptors, Purinergic P2 / Q000235:genetics / Q000378:metabolism*; D058473:Receptors, Purinergic P2Y2; D015398:Signal Transduction / Q000187:drug effects; D019061:src-Family Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism*
C546386:P2ry2 protein, mouse; D047428:Protein Kinase Inhibitors; D034741:RNA, Small Interfering; D018048:Receptors, Purinergic P2; D058473:Receptors, Purinergic P2Y2; C022571:adenosine 5'-O-(3-thiotriphosphate); D000255:Adenosine Triphosphate; D020932:Nerve Growth Factor; D020917:Receptor, trkA; D019061:src-Family Kinases