PAF-induced MAPK activation is inhibited by wortmannin in neutrophils and macrophages.
In the present study we examined the mechanism by which PAF activates MAPK in native cells such as guinea-pig neutrophils and P388D1 macrophage-like cells. We found that PAF activates MAPK through two distinct pathways. One calcium-dependent pathway that likely involves cPKC, and another calcium-independent but wortmannin-sensitive pathway. Using molecular biological methods we are presently examining whether hetrodimeric (p85/p110) type PI 3-kinase is the actual target of wortmannin involved in PAF mediated activation of MAPK.
Ferby
I
I
Department of Biochemistry, Faculty of Medicine, University of Tokyo, Japan.
Waga
I
I
Kume
K
K
Sakanaka
C
C
Shimizu
T
T
D000730:Androstadienes / Q000494:pharmacology*; D000818:Animals; D002118:Calcium / Q000502:physiology; D017868:Cyclic AMP-Dependent Protein Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D004789:Enzyme Activation / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D006168:Guinea Pigs; D066298:In Vitro Techniques; D008264:Macrophages / Q000187:drug effects / Q000201:enzymology*; D009504:Neutrophils / Q000187:drug effects / Q000201:enzymology*; D010972:Platelet Activating Factor / Q000037:antagonists & inhibitors* / Q000502:physiology*; D000077191:Wortmannin
D000730:Androstadienes; D004791:Enzyme Inhibitors; D010972:Platelet Activating Factor; D017868:Cyclic AMP-Dependent Protein Kinases; D002118:Calcium; D000077191:Wortmannin