Abstract
The initiation of saliva formation by parotid acinar cells, which comprise the majority of cells in this salivary gland, is initiated by the release of neurotransmitters (acetylcholine, substance P) from parasympathetic nerves. In response to substance P and the muscarinic agonist carbachol, two ligands that activate phospholipase C-linked receptors, which stimulate fluid secretion, PKC delta was phosphorylated on tyrosine residues. The maximal agonist-dependent tyrosine phosphorylation occurred within seconds of the addition of either agonist and then returned rapidly to a smaller increased level. Phorbol ester also caused a rapid increase in tyrosine phosphorylation, which reached a maximal level 5 min after the addition of phorbol 12-myristate 13-acetate. The increase in tyrosine phosphorylation of PKC delta was blocked by tyrosine kinase inhibitors genistein and staurosporine. Ionophore-mediated elevation of [Ca2+]i or activation of the beta-adrenergic receptor, epidermal growth factor receptor, or insulin receptor did not promote the tyrosine phosphorylation of PKC delta. These results indicate that tyrosine phosphorylation plays a role in early signal transduction events promoted by the activation of muscarinic and substance P receptors and suggests that the tyrosine phosphorylation of PKC delta has a role in the activation of fluid secretion by neurotransmitters binding to phospholipase C-linked receptors.
Highlights
Phospholipids, notably phosphoinositides produced by the activation of phosphatidylinositol 3-kinase, have been found to activate members of the conventional PKC and novel PKC family (Singh et al, 1993; Toker et al, 1994; Nakanishi et al, 1993)
While examining the effects of growth factors and other receptor ligands on the tyrosine phosphorylation pattern of parotid acinar cells, we found that the muscarinic agonist carbachol and substance P promoted the tyrosine phosphorylation of an ~80-kDa protein and that phorbol ester promoted the tyrosine phosphorylation of the same band, which was identified as the 8 isoform ofPKC
The results presented in this study demonstrate that the activation of muscarinic and substance P receptors and phorbol ester stimulated the tyrosine phosphorylation of PKC8 in rat parotid acinar cells
Summary
Vol 270, No 22, Issue of June 2, pp. 13490-13495, 1995 Printed in U.S.A. Carbachol, Substance P, and Phorbol Ester Promote the Tyrosine Phosphorylation of Protein Kinase C8 in Salivary Gland Epithelial Cells*. Ionophore-mediated elevation of [Ca2 + ] i or activation of the f3-adrenergic receptor, epidermal growth factor receptor, or insulin receptor did not promote the tyrosine phosphorylation of PKCB These results indicate that tyrosine phosphorylation plays a role in early signal transduction events promoted by the activation of muscarinic and substance P receptors and suggests that the tyrosine phosphorylation of PKCB has a role in the activation of fluid secretion by neurotransmitters binding to phospholipase C-linked receptors. While examining the effects of growth factors and other receptor ligands on the tyrosine phosphorylation pattern of parotid acinar cells, we found that the muscarinic agonist carbachol and substance P promoted the tyrosine phosphorylation of an ~80-kDa protein and that phorbol ester promoted the tyrosine phosphorylation of the same band, which was identified as the 8 isoform ofPKC. PKC5 in the acinar cells suggests that this biochemical event contributes to the normal physiological responses promoted by the release of neurotransmitters from parasympathetic nerves that promote fluid secretion and saliva formation in this exocrine gland
Sign-in/Register to view highlights & summary 
Published Version (
Free)
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call