5-HT(1A) receptors transactivate the platelet-derived growth factor receptor type beta in neuronal cells

Cell Signal. 2013 Jan;25(1):133-43. doi: 10.1016/j.cellsig.2012.09.021. Epub 2012 Sep 21.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Becaplermin
  • Calcium / metabolism
  • Calcium Signaling
  • Cells, Cultured
  • Humans
  • Mice
  • Mitogen-Activated Protein Kinase 1 / metabolism
  • Mitogen-Activated Protein Kinase 3 / metabolism
  • Neurons / cytology
  • Neurons / metabolism*
  • Pertussis Toxin / pharmacology
  • Phosphorylation / drug effects
  • Proto-Oncogene Proteins c-sis / pharmacology
  • Receptor, Platelet-Derived Growth Factor beta / genetics
  • Receptor, Platelet-Derived Growth Factor beta / metabolism*
  • Receptor, Serotonin, 5-HT1A / metabolism*
  • Serotonin / pharmacology
  • Transcriptional Activation / drug effects
  • Type C Phospholipases / metabolism
  • src-Family Kinases / metabolism

Substances

  • Proto-Oncogene Proteins c-sis
  • Receptor, Serotonin, 5-HT1A
  • Becaplermin
  • Serotonin
  • Pertussis Toxin
  • Receptor, Platelet-Derived Growth Factor beta
  • src-Family Kinases
  • Mitogen-Activated Protein Kinase 1
  • Mitogen-Activated Protein Kinase 3
  • Type C Phospholipases
  • Calcium