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Science 17 October 1997:
Vol. 278. no. 5337, pp. 471 - 474
DOI: 10.1126/science.278.5337.471
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Reports

Inhibition of Phosphatases and Increased Ca2+ Channel Activity by Inositol Hexakisphosphate

Olof Larsson, Christopher J. Barker, Åke Sjöholm, Håkan Carlqvist, Robert H. Michell, Alejandro Bertorello, Thomas Nilsson, Richard E. Honkanen, Georg W. Mayr, Jean Zwiller, Per-Olof Berggren *

Inositol hexakisphosphate (InsP6), the dominant inositol phosphate in insulin-secreting pancreatic beta  cells, inhibited the serine-threonine protein phosphatases type 1, type 2A, and type 3 in a concentration-dependent manner. The activity of voltage-gated L-type calcium channels is increased in cells treated with inhibitors of serine-threonine protein phosphatases. Thus, the increased calcium channel activity obtained in the presence of InsP6 might result from the inhibition of phosphatase activity. Glucose elicited a transient increase in InsP6 concentration, which indicates that this inositol polyphosphate may modulate calcium influx over the plasma membrane and serve as a signal in the pancreatic beta  cell stimulus-secretion coupling.

O. Larsson, C. J. Barker, Å. Sjöholm, A. Bertorello, T. Nilsson, P.-O. Berggren, Rolf Luft Center for Diabetes Research, Department of Molecular Medicine, Karolinska Institute, S-171 76 Stockholm, Sweden.
H. Carlqvist, Astra Pain Control AB, Cellular and Molecular Pharmacology, Novum Unit, S-141 57 Huddinge, Sweden.
R. H. Michell, School of Biochemistry, University of Birmingham, Post Office Box 363, Birmingham B15 2TT, UK.
R. E. Honkanen, Department of Biochemistry, MSB 2198, College of Medicine, University of South Alabama, Mobile, AL 36688, USA.
G. W. Mayr, Institut für Physiologische Chemie, Universitäts-Krankenhaus Eppendorf, 20246 Hamburg, Germany.
J. Zwiller, INSERM U338, 5 rue B. Pascal, 67084 Strasbourg, France.
*   To whom correspondence should be addressed.

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From the Cover: Inositol hexakisphosphate is a physiological signal regulating the K+-inward rectifying conductance in guard cells.
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