Activation of phospholipase D in Chinese hamster ovary cells expressing platelet-activating factor receptor.
Platelet-activating factor (PAF) activated phospholipase D (PLD) in WT-H cells, CHO cells stably expressing cloned guinea-pig PAF receptor. The PLD activation was found to be dependent on extracellular Ca2+, protein kinase C (PKC), and a currently unidentified protein tyrosine kinase (PTK). PTK inhibitors ST-638 and genistein inhibited PLD activation induced by PAF as well as phorbol myristate acetate, indicating that PTK acts downstream of PKC. Furthermore, activation of MAP (mitogen-activated protein) kinases, as assessed by their phosphorylation, was also dependent on Ca2+, PKC, and PTK. The correlation between PLD activity and MAP kinase activation, together with the previously observed MAP kinase activation associated with arachidonic acid release by cPLA2 [Honda et al. (1994) J. Biol. Chem. 269, 2307-2315], led us to examine the involvement of MAP kinase in PLD activation. The results indicate that PLD and MAP kinases are activated through the common pathway consisting of Ca2+, PKC, and the unidentified PTK, which act in parallel, but not in a linear sequence.
Liu
B
B
Department of Biochemistry, Gifu University School of Medicine.
Nakashima
S
S
Kanoh
H
H
Takano
T
T
Shimizu
T
T
Nozawa
Y
Y
D000818:Animals; D016466:CHO Cells / Q000201:enzymology* / Q000648:ultrastructure*; D002118:Calcium / Q000494:pharmacology; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000037:antagonists & inhibitors / Q000502:physiology; D006224:Cricetinae; D015536:Down-Regulation / Q000502:physiology; D004789:Enzyme Activation; D004790:Enzyme Induction; D006168:Guinea Pigs; D007700:Kinetics; D010739:Phospholipase D / Q000037:antagonists & inhibitors / Q000378:metabolism*; D010766:Phosphorylation; D010972:Platelet Activating Factor / Q000494:pharmacology; D010980:Platelet Membrane Glycoproteins / Q000502:physiology*; D011493:Protein Kinase C / Q000037:antagonists & inhibitors / Q000378:metabolism / Q000502:physiology; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism / Q000502:physiology; D011956:Receptors, Cell Surface; D043562:Receptors, G-Protein-Coupled; D013268:Stimulation, Chemical
D010972:Platelet Activating Factor; D010980:Platelet Membrane Glycoproteins; D011956:Receptors, Cell Surface; D043562:Receptors, G-Protein-Coupled; C039351:platelet activating factor receptor; D011505:Protein-Tyrosine Kinases; D011493:Protein Kinase C; D017871:Calcium-Calmodulin-Dependent Protein Kinases; D010739:Phospholipase D; D002118:Calcium