Jump to ContentJump to Main Navigation
Show Summary Details

Biological Chemistry

Editor-in-Chief: Brüne, Bernhard

Editorial Board Member: Buchner, Johannes / Lei, Ming / Ludwig, Stephan / Sies, Helmut / Turk, Boris / Wittinghofer, Alfred

SCImago Journal Rank (SJR) 2015: 1.607
Source Normalized Impact per Paper (SNIP) 2015: 0.751
Impact per Publication (IPP) 2015: 2.609

249,00 € / $374.00 / £187.00*

See all formats and pricing



Select Volume and Issue


30,00 € / $42.00 / £23.00

Get Access to Full Text

Two Different Mechanisms for Activation of Cyclic PIP Synthase: by a G Protein or by Protein Tyrosine Phosphorylation

Heinrich K. Wasner / Marion Gebel / Sabine Hucken / Monika Schaefer / Monika Kincses

Citation Information: Biological Chemistry. Volume 381, Issue 2, Pages 145–153, ISSN (Print) 1431-6730, DOI: 10.1515/BC.2000.020, June 2005

Publication History

Published Online:


The biosynthesis of the functional, endogenous cyclic AMP antagonist, prostaglandylinositol cyclic phosphate (cyclic PIP) is performed by the plasma membrane bound enzyme cyclic PIP synthase, which combines prostaglandin E (PGE) and activated inositol phosphate (nIP) to cyclic PIP. The K values of the enzyme for the substrates PGE and nIP are in the micromolar range. The plasma membranebound synthase is activated by fluoride, by the stable GTP analog GMPPNP, by protamine or biguanide, by noradrenaline, and by insulin. The activation by protamine or biguanide and fluoride (10m) is additive, which may indicate the presence of two different types of enzyme, comparable to phospholipase Cβ and phospholipase Cγ. Plasma membranebound cyclic PIP synthase is inhibited by the protein tyrosine kinase inhibitor tyrphostin B46 with an IC[50] of 1.7. However, the solubilized and gelfiltrated enzyme is no longer inhibited by tyrphostin, indicating that the activity of cyclic PIP synthase is connected with the activity of a membranebound protein tyrosine kinase. Cyclic PIP synthase activity of freshly prepared plasma membranes is unstable. Upon freezing and rethawing of liver plasma membranes, this instability is increased about 2-fold. Protein tyrosine phosphatase inhibitors [vanadate, fluoride (50 100m)] stabilize the enzyme activity, but protease inhibitors do not, indicating that inactivation of the enzyme is connected with protein tyrosine dephosphorylation. Cyclic PIP synthase is present in all tissues tested, like brain, heart, intestine, kidney, liver, lung, skeletal muscle, spleen, and testis. Apart from liver, cyclic PIP synthase activity in most tissues is rather low, but it can be increased up to 5-fold when protein tyrosine phosphatase inhibitors like vanadate are present in the homogenization buffer. Preincubation of cyclic PIP synthase of liver plasma membranes with the tyrosine kinase src kinase causes a 2-fold increase of cyclic PIP synthase activity, though this is certainly not the physiological role played by src kinase in intact cells. The data indicate that cyclic PIP synthase can be activated by two separate mechanisms: by a G protein or by protein tyrosine phosphorylation.

Citing Articles

Here you can find all Crossref-listed publications in which this article is cited. If you would like to receive automatic email messages as soon as this article is cited in other publications, simply activate the “Citation Alert” on the top of this page.

P.N. Shashkin, T. Meckmongkol, H.K. Wasmer, B.C. Hansen, and H.K. Ortmeyel
Journal of Basic and Clinical Physiology and Pharmacology, 2001, Volume 12, Number 1, Page 1
S. Weber, H. Lemoine, and H.K. Wasner
Biological Chemistry, 2000, Volume 381, Number 5-6
Pavel N. Shashkin, Heinrich K. Wasner, Heidi K. Ortmeyer, and Barbara C. Hansen
Diabetes/Metabolism Research and Reviews, 2001, Volume 17, Number 4, Page 273

Comments (0)

Please log in or register to comment.