Tyrosine phosphorylation is involved in receptor coupling to phospholipase D but not phospholipase C in the human neutrophil.
The tyrosine kinase inhibitors ST271, ST638 and erbstatin inhibited phospholipase D (PLD) activity in human neutrophils stimulated by fMet-Leu-Phe, platelet-activating factor and leukotriene B4. These compounds did not inhibit phorbol ester-stimulated PLD, indicating that they do not inhibit PLD per se, but probably act at a site between the receptor and the phospholipase. In contrast, the protein kinase C inhibitor Ro-31-8220 inhibited phorbol 12,13-dibutyrate- but not fMet-Leu-Phe-stimulated PLD activity, arguing against the involvement of protein kinase C in the receptor-mediated activation of PLD. ST271 did not inhibit Ins(1,4,5)P3 generation, but did inhibit protein tyrosine phosphorylation stimulated by fMet-Leu-Phe. The phosphotyrosine phosphatase inhibitor pervanadate increased tyrosine phosphorylation and stimulated PLD. These results suggest that tyrosine kinase activity is involved in receptor coupling to PLD but not to PtdIns(4,5)P2-specific phospholipase C in the human neutrophil.
Cell Signalling Group, Biochemical Sciences, Wellcome Research Laboratories, Kent, U.K.
I J
IJ
Uings
N T
NT
Thompson
R W
RW
Randall
G D
GD
Spacey
R W
RW
Bonser
A T
AT
Hudson
L G
LG
Garland
D004789:Enzyme Activation; D006801:Humans; D007211:Indoles; D009240:N-Formylmethionine Leucyl-Phenylalanine / Q000494:pharmacology; D009504:Neutrophils / Q000187:drug effects / Q000201:enzymology*; D015240:Phorbol 12,13-Dibutyrate / Q000494:pharmacology; D043265:Phosphatidylinositol Diacylglycerol-Lyase; D010739:Phospholipase D / Q000378:metabolism*; D010727:Phosphoric Diester Hydrolases / Q000378:metabolism; D010766:Phosphorylation; D019000:Phosphotyrosine; D011493:Protein Kinase C / Q000037:antagonists & inhibitors / Q000494:pharmacology; D011505:Protein-Tyrosine Kinases / Q000378:metabolism*; D011956:Receptors, Cell Surface / Q000502:physiology*; D010738:Type C Phospholipases / Q000378:metabolism*; D014443:Tyrosine / Q000031:analogs & derivatives* / Q000378:metabolism
D007211:Indoles; D011956:Receptors, Cell Surface; D019000:Phosphotyrosine; D015240:Phorbol 12,13-Dibutyrate; D014443:Tyrosine; D009240:N-Formylmethionine Leucyl-Phenylalanine; D011505:Protein-Tyrosine Kinases; D011493:Protein Kinase C; D010727:Phosphoric Diester Hydrolases; D010738:Type C Phospholipases; D010739:Phospholipase D; D043265:Phosphatidylinositol Diacylglycerol-Lyase; C064758:Ro 31-8220