Activation of cytosolic phospholipase A2 by transforming growth factor-alpha in HEL-30 keratinocytes.
In the mouse keratinocyte line HEL-30 the epidermal mitogen transforming growth factor-alpha (TGF-alpha) stimulated the rapid release of arachidonic acid in a dose- and time-dependent manner. The liberation of arachidonic acid was due to the activation of a Ca(2+)-dependent cytosolic phospholipase A2 (cPLA2). The activation mechanism critically depended on a functionally active epidermal growth factor receptor tyrosine kinase and occurred independently of phospholipase C-mediated increases in cellular diacylglycerol and inositol 1,4,5-trisphosphate concentrations and protein kinase C activation. The activation included an increase in cytosolic PLA2 (cPLA2) activity and an association of the enzyme with the membrane fraction. Both activation steps apparently occurred in the presence of basal cytoplasmic Ca2+ concentrations. Moreover, cPLA2 or a closely associated protein was found to be phosphorylated on tyrosine upon TGF-alpha challenge of the cells. The data suggest that tyrosine phosphorylation is involved in the TGF-alpha-induced activation of cPLA2.
Kast
R
R
Research Program Tumor Cell Regulation, German Cancer Research Center, Heidelberg.
Fürstenberger
G
G
Marks
F
F
D000818:Animals; D001095:Arachidonic Acids / Q000378:metabolism; D001692:Biological Transport; D002118:Calcium / Q000378:metabolism; D002460:Cell Line; D003600:Cytosol / Q000201:enzymology; D004789:Enzyme Activation; D066246:ErbB Receptors / Q000378:metabolism; D006801:Humans; D015603:Keratinocytes / Q000166:cytology / Q000201:enzymology*; D051379:Mice; D010741:Phospholipases A / Q000378:metabolism*; D054467:Phospholipases A2; D010766:Phosphorylation; D011233:Precipitin Tests; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D016211:Transforming Growth Factor alpha / Q000494:pharmacology*; D014443:Tyrosine / Q000378:metabolism
D001095:Arachidonic Acids; D016211:Transforming Growth Factor alpha; D014443:Tyrosine; D066246:ErbB Receptors; D011505:Protein-Tyrosine Kinases; D010741:Phospholipases A; D054467:Phospholipases A2; D013755:Tetradecanoylphorbol Acetate; D002118:Calcium