β-adrenergic-responsive activation of extracellular signal-regulated protein kinases in salivary cells: Role of epidermal growth factor receptor and cAMP

Chih Ko Yeh, Paramita M Ghosh, Howard Dang, Qun Liu, Alan L. Lin, Bin Xian Zhang, Michael S. Katz

Research output: Contribution to journalArticle

18 Citations (Scopus)

Abstract

The β-adrenergic receptor agonist isoproterenol exerts growth-promoting effects on salivary glands. In this study, activation of ERKs. members of the mitogen-activated protein kinase family, by isoproterenol was examined in a human salivary gland cell line (HSY). Immunoblot analysis indicated that isoproterenol (10-5 M) induced transient activation of ERK1/2 (4.4-fold relative to basal at 10 min) similar to that caused by EGF (6.7 fold). Isoproterenol, like EGF, also induced phosphorylation of the EGF receptor. However, inhibition of EGF receptor phosphorylation by the tyrphostin AG-1478 only partially attenuated isoproterenol-induced ERK phosphorylation, whereas EGF-responsive ERK activation was completely blocked. The Gi inhibitor pertussis toxin also caused partial inhibition of isoproterenol- stimulated ERK activation. The cAMP analog 8-(4-chlorophenylthio)adenosine 3′,5′-cyclic monophosphate (CPT-cAMP) and the cAMP-elevating agents IBMX and cholera toxin produced transient ERK1/2 activation, similar to the effect of isoproterenol, in HSY cells. The stimulatory effects of isoproterenol and cAMP on ERK phosphorylation were not reduced by the PKA inhibitor H-89, whereas the Src family inhibitor 4-amino-5-(4-chlorophenyl)-7-(t-butyl) pyrazolo[3,4-d]pyrimidase (PP2) and transfection of a dominant-negative Src construct diminished isoproterenol-induced ERK activation. Isoproterenol induced marked over-expression of the cell growth-related adhesion molecule CD44, and this effect of isoproterenol was abolished by the ERK pathway inhibitor PD-98059. In summary, we show a dual mechanism of isoproterenol-induced ERK phosphorylation in HSY cells-one pathway mediated by EGF receptor transactivation and the other by an EGF receptor-independent pathway possibly mediated by cAMP. Our results also suggest that isoproterenol-induced growth of salivary tissue may involve ERK-mediated CD44 expression.

Original languageEnglish (US)
JournalAmerican Journal of Physiology - Cell Physiology
Volume288
Issue number6 57-6
DOIs
StatePublished - Jun 2005
Externally publishedYes

Fingerprint

Extracellular Signal-Regulated MAP Kinases
Isoproterenol
Epidermal Growth Factor Receptor
Adrenergic Agents
Protein Kinases
Chemical activation
Phosphorylation
Epidermal Growth Factor
Salivary Glands
Growth
1-Methyl-3-isobutylxanthine
Adrenergic Agonists
MAP Kinase Signaling System
Cholera Toxin
Pertussis Toxin
Cell growth
Mitogen-Activated Protein Kinases
Adenosine
Transcriptional Activation
Transfection

Keywords

  • CD44
  • Mitogen-activated protein kinase

ASJC Scopus subject areas

  • Clinical Biochemistry
  • Cell Biology
  • Physiology

Cite this

β-adrenergic-responsive activation of extracellular signal-regulated protein kinases in salivary cells : Role of epidermal growth factor receptor and cAMP. / Yeh, Chih Ko; Ghosh, Paramita M; Dang, Howard; Liu, Qun; Lin, Alan L.; Zhang, Bin Xian; Katz, Michael S.

In: American Journal of Physiology - Cell Physiology, Vol. 288, No. 6 57-6, 06.2005.

Research output: Contribution to journalArticle

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T2 - Role of epidermal growth factor receptor and cAMP

AU - Yeh, Chih Ko

AU - Ghosh, Paramita M

AU - Dang, Howard

AU - Liu, Qun

AU - Lin, Alan L.

AU - Zhang, Bin Xian

AU - Katz, Michael S.

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AB - The β-adrenergic receptor agonist isoproterenol exerts growth-promoting effects on salivary glands. In this study, activation of ERKs. members of the mitogen-activated protein kinase family, by isoproterenol was examined in a human salivary gland cell line (HSY). Immunoblot analysis indicated that isoproterenol (10-5 M) induced transient activation of ERK1/2 (4.4-fold relative to basal at 10 min) similar to that caused by EGF (6.7 fold). Isoproterenol, like EGF, also induced phosphorylation of the EGF receptor. However, inhibition of EGF receptor phosphorylation by the tyrphostin AG-1478 only partially attenuated isoproterenol-induced ERK phosphorylation, whereas EGF-responsive ERK activation was completely blocked. The Gi inhibitor pertussis toxin also caused partial inhibition of isoproterenol- stimulated ERK activation. The cAMP analog 8-(4-chlorophenylthio)adenosine 3′,5′-cyclic monophosphate (CPT-cAMP) and the cAMP-elevating agents IBMX and cholera toxin produced transient ERK1/2 activation, similar to the effect of isoproterenol, in HSY cells. The stimulatory effects of isoproterenol and cAMP on ERK phosphorylation were not reduced by the PKA inhibitor H-89, whereas the Src family inhibitor 4-amino-5-(4-chlorophenyl)-7-(t-butyl) pyrazolo[3,4-d]pyrimidase (PP2) and transfection of a dominant-negative Src construct diminished isoproterenol-induced ERK activation. Isoproterenol induced marked over-expression of the cell growth-related adhesion molecule CD44, and this effect of isoproterenol was abolished by the ERK pathway inhibitor PD-98059. In summary, we show a dual mechanism of isoproterenol-induced ERK phosphorylation in HSY cells-one pathway mediated by EGF receptor transactivation and the other by an EGF receptor-independent pathway possibly mediated by cAMP. Our results also suggest that isoproterenol-induced growth of salivary tissue may involve ERK-mediated CD44 expression.

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