Myosin light chain phosphorylation controls insulin secretion at a
proximal step in the secretory cascade.
Iida, Yuji, Takao Senda, Yoshihisa Matsukawa,koji Onoda, Jun-Ichi
Miyazaki, Hiromi Sakaguchi, Yuji Nimura, Hiroyoshi Hidaka, and Ichiro
Niki.
Department of Pharmacology, First Department of Surgery and
Department of Anatomy, Nagoya University School of Medicine, Nagoya,
Department of Thoracic Surgery, Faculty of Medicine, Mie University,
Tsu and Institute of Development, Aging and Cancer, Tohoku
University, Sendai, Japan
APStracts 4:0137E, 1997.
The aim of this study was to investigate how insulin secretion is
controlled by phosphorylation of the myosin light chain (MLC). Ca2+
-evoked insulin release from pancreatic islets permeabilized with
streptolysin-O was inhibited by different monoclonal antibodies
against myosin light chain kinase (MLCK) to extents parallel to their
inhibition of purified MLCK. Anti-MLCK antibody also inhibited
insulin release caused by the stable GTP analogue, GTP[gamma]S, even
at a substimulatory concentration (0.1[mu]M) of Ca2+. Free Ca2+
increased MLC peptide phosphorylation by [beta]-cell extracts in
vitro. In contrast to the phosphorylation by purified MLCK or by CaM
kinase II, the activity partially remained with [beta]-cell under
non-stimulatory Ca2+ (0.1[mu]M) conditions. The MLCK inhibitor, ML-9,
inhibited the activity in the [beta]-cell with both substimulatory or
stimulatory Ca2+, whereas KN-62, an inhibitor of CaM kinase II, only
exerted an influence in the latter case. ML-9 decreased intracellular
granule movement in MIN6 cells under basal and acetylcholine
-stimulated conditions. We propose that MLC phosphorylation may
modulate translocation of secretory granules, resulting in enhanced
insulin secretion.
Received 31 December 1996; accepted in final form 20 June 1997.
APS Manuscript Number E633-6.
Article publication pending Am. J. Physiol. (Endocrinol. Metab.).
ISSN 1080-4757 Copyright 1997 The American Physiological Society.
Published in APStracts on 10 July 1997