Calcium, phospholipid turnover and transmembrane signalling.
Turnover of phosphatidylinositol, which is provoked by various neurotransmitters, peptide hormones and many other biologically active substances, appears to serve as a signal for the transmembrane control of protein phosphorylation through activation of a novel protein kinase (C-kinase). The activation of this enzyme absolutely requires Ca2+ and phosphatidylserine. Diacylglycerol derived from the receptor-linked breakdown of phosphatidylinositol dramatically increases the affinity of C-kinase for Ca2+, and thereby renders this enzyme fully active without a net increase in the concentration of Ca2+. Under appropriate conditions synthetic diacylglycerol directly added to intact cell systems activates C-kinase fully without interaction with surface receptors. By using such synthetic diacylglycerol and the Ca2+ ionophore A23187, it is shown that either receptor-linked protein phosphorylation or Ca2+ mobilization alone is merely a prerequisite but not a sufficient requirement, and both are synergistically effective for causing a full physiological cellular response. In some tissues cyclic nucleotides, both cyclic AMP and cyclic GMP, may inhibit the receptor-linked breakdown of phosphatidylinositol, and appear to provide negative control that prevents over-response.
D000527:Alprostadil; D000818:Animals; D003994:Bucladesine / Q000494:pharmacology; D000001:Calcimycin / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism*; D002462:Cell Membrane / Q000378:metabolism*; D000242:Cyclic AMP / Q000378:metabolism; D006152:Cyclic GMP / Q000378:metabolism; D008954:Models, Biological; D010718:Phosphatidylserines / Q000378:metabolism; D010743:Phospholipids / Q000378:metabolism*; D011458:Prostaglandins E / Q000494:pharmacology; D011494:Protein Kinases / Q000378:metabolism
D010718:Phosphatidylserines; D010743:Phospholipids; D011458:Prostaglandins E; D000001:Calcimycin; D003994:Bucladesine; D000242:Cyclic AMP; D011494:Protein Kinases; D000527:Alprostadil; D006152:Cyclic GMP; D002118:Calcium