Inhibition by phospholipids, lysophospholipids and gangliosides of melittin-induced phosphorylation in bovine mammary gland.
Melittin, a toxic peptide from bee venom known to inhibit protein kinase C (PKC) activity, induces, like sphingosine, phosphorylation of proteins, such as the 19 kDa and 27 kDa, in bovine mammary gland. This phosphorylation is inhibited by the addition of phosphatidylserine (PS). The present study was conducted to examine whether phospholipids (other than PS), lysophospholipids and gangliosides can inhibit the phosphorylation of cytosolic proteins from bovine mammary gland. The lipid effects were also explored in the sphingosine-induced phosphorylation for comparison. Like PS, phosphatidic acid, phosphatidylglycerol and phosphatidylinositol inhibited the melittin-induced phosphorylation. Phosphatidylcholine was less potent and phosphatidylethanolamine was inactive in inhibiting the phosphorylation. Similar results were obtained when sphingosine was used instead of melittin. Of the lysophospholipids tested, lysophosphatidic acid was most effective in inhibiting the phosphorylation induced by melittin. Lysophosphatidylcholine was inactive in reversing the melittin-induced phosphorylation, but it selectively suppressed the 19 kDa phosphorylation induced by sphingosine. Gangliosides inhibited both melittin- and sphingosine-induced phosphorylation and their effectiveness was: GT1b > GD1a = GD3 > GM3. Of the phosphoproteins, the 19 kDa was most sensitive to ganglioside inhibition. These results suggest that melittin-induced phosphorylation is selectively inhibited by specific lipids and also that the enzyme(s) responsible for the phosphorylation is not identical to the sphingosine-activated protein kinases.
Katoh
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Laboratory of Biochemistry, National Institute of Animal Health, Ibaraki, Japan.
D000818:Animals; D002417:Cattle; D004305:Dose-Response Relationship, Drug; D005260:Female; D005732:Gangliosides / Q000494:pharmacology*; D008246:Lysophospholipids / Q000494:pharmacology*; D008321:Mammary Glands, Animal / Q000187:drug effects* / Q000378:metabolism; D008555:Melitten / Q000633:toxicity*; D008970:Molecular Weight; D010712:Phosphatidic Acids / Q000494:pharmacology; D010713:Phosphatidylcholines / Q000494:pharmacology; D010714:Phosphatidylethanolamines / Q000494:pharmacology; D010715:Phosphatidylglycerols / Q000494:pharmacology; D010716:Phosphatidylinositols / Q000494:pharmacology; D010718:Phosphatidylserines / Q000494:pharmacology; D010743:Phospholipids / Q000494:pharmacology*; D010766:Phosphorylation; D011493:Protein Kinase C / Q000378:metabolism; D013110:Sphingosine / Q000633:toxicity; D013329:Structure-Activity Relationship; D013379:Substrate Specificity
D005732:Gangliosides; D008246:Lysophospholipids; D010712:Phosphatidic Acids; D010713:Phosphatidylcholines; D010714:Phosphatidylethanolamines; D010715:Phosphatidylglycerols; D010716:Phosphatidylinositols; D010718:Phosphatidylserines; D010743:Phospholipids; D008555:Melitten; D011493:Protein Kinase C; D013110:Sphingosine