Gastric mucin secretion in response to beta-adrenergic G protein-coupled receptor activation is mediated by SRC kinase-dependent epidermal growth factor receptor transactivation

• Autorzy: Slomiany B.L. , Slomiany A.
• Języki publikacji: EN

Abstrakty

EN

In many systems, the integration of converging regulatory signals that relay on G protein-coupled receptor (GPCR) activation into functional cellular pathways requires the involvement of receptor tyrosine kinase. In this report, we provide evidence that activation of GPCR by ß-adrenergic agonist leading to stimulation in gastric mucin secretion requires epidermal growth factor receptor (EGFR) participation. Using [3H]glucosamine-labeled gastric mucosal cells, we show that stimulatory effect of ß-adrenergic agonist, isoproterenol, on mucin secretion was inhibited by EGFR kinase inhibitor, PD153035, as well as wortmannin, a specific inhibitor of PI3K. Both inhibitors, moreover, blunted the mucin secretory responses to ß-adrenergic agonist-generated second messenger, cAMP as well as adenylate cyclase activator, forskolin. The gastric mucin secretory responses to isoproterenol, furthermore, were inhibited by PP2, a selective inhibitor of tyrosine kinase Src responsible for ligand-independent EGFR autophosphorylation, but not by ERK inhibitor, PD98059. The inhibition of ERK, moreover, did not cause attenuation in mucin secretion in response to cAMP and forskolin. The findings underline the role of EGFR as a convergence point in gastric mucin secretion triggered by ß-adrenergic GPCR activation, and demonstrate the requirement for Src kinase in EGFR transactivation.

Słowa kluczowe

EN

epidermal growth factor; gastric mucin; transactivation; beta-adrenergic G protein-coupled receptor; secretion

• Wydawca: -
• Czasopismo: Journal of Physiology and Pharmacology
• Rocznik: 2005
• Tom: 56
• Numer: 2
• Opis fizyczny: p.247-258,fig.,ref.

Twórcy

autor

Slomiany B.L.

• Research Center University of Medicine and Dentistry of New Jersey, Newark, NJ 07103-2400, USA

autor

Slomiany A.