Differential modulation of protein kinase C isozymes in rat parotid acinar cells: Relation to amylase secretion

We investigated the expression, distribution, and activation parameters of protein kinase C (PKC) isozymes in isolated rat parotid acinar cells. By analyzing cellular extracts by western blot analysis and for isozyme-specific RNA, the Ca 2+independent PKC-δ, -ϵ, and -ζ were detected in the cytosolic...

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Veröffentlicht in:Biochemical pharmacology 1996-08, Vol.52 (4), p.569-577
Hauptverfasser: Terzian, A.Roger, Zhang, Xuejun, Rubin, Ronald P.
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Sprache:eng
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Zusammenfassung:We investigated the expression, distribution, and activation parameters of protein kinase C (PKC) isozymes in isolated rat parotid acinar cells. By analyzing cellular extracts by western blot analysis and for isozyme-specific RNA, the Ca 2+independent PKC-δ, -ϵ, and -ζ were detected in the cytosolic, particulate (plasma membrane), and nuclear fractions of unstimulated cells, whereas the Ca 2+-dependent PKC-α was confined to the cytosolic and particulate fractions. The expressed isozymes showed distinct responses to phorbol 12-myristate 13-acetate (PMA), thymeleatoxin, and cell surface receptor agonists with respect to translocation from cytosol to particulate fraction and nucleus, as well as sensitivity to down-regulation caused by prolonged exposure to PMA (3–20 hr). The marked susceptibility to down-regulation displayed by PKC-α and -δ was accompanied by an enhanced secretory response to norepinephrine as compared with control cells. Further, the selective PKC inhibitors Ro 31-8220 and CGP 41 251 also produced a concentration-dependent enhancement of norepinephrine-induced amylase secretion. Our findings suggest that PKC-α or -δ plays a negative modulatory role, rather than an obligatory role, in amylase secretion. Also, the localization and redistribution of PKC-ϵ and -δ to the nucleus by PKC activators imply that one or both of these isozymes may regulate such processes as cellular proliferation and/or differentiation. BiocHEM pharmacol 52;4:569–577, 1996.
ISSN:0006-2952
1873-2968
DOI:10.1016/0006-2952(96)00308-5