title: 5-HT(1A) receptors transactivate the platelet-derived growth factor receptor type beta in neuronal cells.
abstract: In the absence of ligand, certain growth factor receptors can be activated via G-protein coupled receptor (GPCR) activation in a process termed transactivation. Serotonin (5-HT) receptors can transactivate platelet-derived growth factor (PDGF) β receptors in smooth muscle cells, but it is not known if similar pathways occur in neuronal cells. Here we show that 5-HT can transiently increase the phosphorylation of PDGFβ receptors through 5-HT(1A) receptors in a time- and dose-dependent manner in SH-SY5Y neuroblastoma cells. 5-HT also transactivates PDGFβ receptors in primary cortical neurons. This transactivation pathway is pertussis-toxin sensitive and Src tyrosine kinase-dependent. This pathway is also dependent on phospholipase C activity and intracellular calcium signaling. Several studies involving PDGFβ receptor transactivation by GPCRs have also demonstrated a PDGFβ receptor-dependent increase in the phosphorylation of ERK1/2. Yet in SH-SY5Y cells, 5-HT treatment causes a PDGFβ receptor-independent increase in ERK1/2 phosphorylation. This crosstalk between 5-HT and PDGFβ receptors identifies a potentially important signaling link between the serotonergic system and growth factor signaling in neurons.
authors.affiliation: Department of Biology, University of Waterloo, Canada.
authors.forename: Jeff S
authors.initials: JS
authors.lastname: Kruk
authors.forename: Maryam S
authors.initials: MS
authors.lastname: Vasefi
authors.forename: Hui
authors.initials: H
authors.lastname: Liu
authors.forename: John J
authors.initials: JJ
authors.lastname: Heikkila
authors.forename: Michael A
authors.initials: MA
authors.lastname: Beazely
mesh_terms: D000818:Animals; D000077214:Becaplermin; D002118:Calcium / Q000378:metabolism; D020013:Calcium Signaling; D002478:Cells, Cultured; D006801:Humans; D051379:Mice; D019950:Mitogen-Activated Protein Kinase 1 / Q000378:metabolism; D048052:Mitogen-Activated Protein Kinase 3 / Q000378:metabolism; D009474:Neurons / Q000166:cytology / Q000378:metabolism*; D037342:Pertussis Toxin / Q000494:pharmacology; D010766:Phosphorylation / Q000187:drug effects; D020574:Proto-Oncogene Proteins c-sis / Q000494:pharmacology; D020797:Receptor, Platelet-Derived Growth Factor beta / Q000235:genetics / Q000378:metabolism*; D044282:Receptor, Serotonin, 5-HT1A / Q000378:metabolism*; D012701:Serotonin / Q000494:pharmacology; D015533:Transcriptional Activation / Q000187:drug effects; D010738:Type C Phospholipases / Q000378:metabolism; D019061:src-Family Kinases / Q000378:metabolism
chemical_list: D020574:Proto-Oncogene Proteins c-sis; D044282:Receptor, Serotonin, 5-HT1A; D000077214:Becaplermin; D012701:Serotonin; D037342:Pertussis Toxin; D020797:Receptor, Platelet-Derived Growth Factor beta; D019061:src-Family Kinases; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3; D010738:Type C Phospholipases; D002118:Calcium