Epidermal growth factor upregulates β-adrenergic receptor signaling in a human salivary cell line

Chih Ko Yeh, Tazuko K. Hymer, April L. Sousa, Bin Xian Zhang, Meyer D. Lifschitz, Michael S. Katz

Research output: Contribution to journalArticlepeer-review

10 Scopus citations


The effects of epidermal growth factor (EGF) on the β-adrenergic receptor-coupled adenylyl cyclase system were studied in a human salivary cell line (HSY). The β-adrenergic agonist isoproterenol (10-5 M) stimulated adenylyl cyclase activity by ∼2-fold, and the isoproterenol response was increased 1.8-fold after prolonged (48 h) exposure to EGF (5 × 10-10 M). In contrast, enzyme activation via stimulatory prostaglandin receptors and by agents acting on nonreceptor components of the adenylyl cyclase system was not enhanced by EGF. β-Adrenergic receptor density, assessed by binding of the β-adrenergic receptor antagonist (-)-[125I]iodopindolol, was increased threefold after EGF treatment. Competition binding studies with unlabeled antagonists selective for β1- and β2-adrenergic receptor subtypes indicated that the increase in (-)-[125I] iodopindolol binding sites induced by EGF reflected an increased number of β2-adrenergic receptors. Likewise, Northern blot analysis of RNA from EGF-treated cells revealed selective induction of β2-adrenergic receptor mRNA, which was blocked by the RNA synthesis inhibitor actinomycin D. The increase in β-adrenergic receptor density produced by EGF was unaltered after phorbol ester-induced downregulation of protein kinase C (PKC). Enhancement of isoproterenol-responsive adenylyl cyclase activity and phosphorylation of mitogen-activated protein kinase (MAPK) by EGF were both blocked by the MAPK pathway inhibitor PD-98059. The results suggest that in HSY cells EGF enhances β-adrenergic responsiveness by upregulating β2-adrenergic receptor expression at the transcriptional level. Moreover, the stimulatory effect of EGF on β2-adrenergic receptor signaling appears to be mediated by the MAPK pathway and independent of PKC activation.

Original languageEnglish (US)
Pages (from-to)C1164-C1175
JournalAmerican Journal of Physiology - Cell Physiology
Issue number5 53-5
StatePublished - May 1 2003


  • Adenylyl cyclase
  • G protein-coupled receptor
  • Mitogen-activated protein kinase
  • Protein kinase C
  • Signal transduction

ASJC Scopus subject areas

  • Physiology
  • Cell Biology


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