Lacrimal gland pkc isoforms are differentially involved in agonist -induced protein secretion. Zoukhri, Driss, Robin R. Hodges, Christian Sergheraert, Alex Toker, and Darlene A. Dartt. Schepens Eye Research Institute and Harvard Medical School, 20 Staniford St., Boston, MA 02114, Institut Pasteur de Lille, URA CNRS 1309, B.P. 245, 59019 Lille, France, Department of Medicine, Division of Signal Transduction, Beth Israel Hospital, Boston, MA 02115
APStracts 3:0253C, 1996.
In the present study, we have synthesized and N-myristoylated peptides derived from the pseudosubstrate sequences of PKC , - , and - (myr -PKC [15-28], myr-PKC [142-153], and myr-PKC [149-164]), three isoforms present in rat lacrimal gland and a peptide derived from the sequence of the endogenous inhibitor (myr-PKI[17-25]) of protein kinase A (PKA). Lacrimal gland acini were preincubated for 60 min with the myristoylated peptides (10-10 M - 3 x 10-7 M), then protein secretion was stimulated with either a phorbol ester, phorbol 12,13 -dibutyrate (PdBu, 10-6 M); vasoactive intestinal peptide (VIP, 10-8 M); a cholinergic agonist, carbachol (10-5 M); or an 1-adrenergic agonist, phenylephrine ( 10-4 M) for 20 min. In intact lacrimal gland acini myr-PKC [15-28] and myr-PKC [149-164], and to a lesser extent myr-PKC [142-153], inhibited PdBu-induced protein secretion. This effect was not reproduced either by the acetylated peptide or by the myristoylated PKI which inhibited VIP-induced protein secretion, a response mediated by PKA. Carbachol-induced protein secretion was inhibited by all three peptides. In contrast, phenylephrine-induced protein secretion was inhibited only by myr-PKC [149-164], whereas myr-PKC [15-28] and myr-PKC [142-153] had a stimulatory effect. Neither myristoylated peptide affected the calcium increase evoked by cholinergic or 1-adrenergic agonists. We concluded that phorbol ester- and receptor-induced protein secretion involve different PKC isoforms in lacrimal gland. 

Received 14 May 1996; accepted in final form 16 July 1996.
APS Manuscript Number C262-6.
Article publication pending Am. J. Physiol. (Cell Physiology).
ISSN 1080-4757 Copyright 1996 The American Physiological Society.
Published in APStracts on 21 August 1996