Involvement of phosphatidylinositol 3-kinase in Fc gamma receptor signaling.
Wortmannin, a potent and selective inhibitor of phosphatidylinositol (PI) 3-kinase (Okada, T., Sakuma, L., Fukui, Y., Hazeki, O., and Ui, M. (1994) J. Biol. Chem. 269, 3563-3567), prevented Fc receptor for IgG (Fc gamma R)-dependent phagocytosis of the human monocytic cell line U937 or guinea pig neutrophils. Cross-linking of Fc gamma R on the surface of U937 cells increased PI 3-kinase activity that was immunoprecipitated with antibody against phosphotyrosine or antibody against the 85-kDa regulatory subunit of PI 3-kinase. Specific cross-linking of Fc gamma R subclass Fc gamma RI or Fc gamma RII, using monoclonal antibodies against each receptor subclass and the F(ab')2 fragment of goat antibody against mouse IgG, increased anti-phosphotyrosine-precipitable PI 3-kinase activity. Treatment of cells with anti-Fc gamma RIII antibody plus the same F(ab')2 did not affect the activity, reflecting the lack of Fc gamma RIII in U937 cells. Fcy gamma R stimulation triggered prominent tyrosine phosphorylation of several proteins, among which the 115-kDa peptide showed strong association with PI 3-kinase. Thus, Fc gamma R appears to be coupled functionally, via a tyrosine kinase, to PI 3-kinase, which may regulate the phagocytotic activity of the cells.
Ninomiya
N
N
Ui Laboratory, Institute of Physical and Chemical Research, Wako-shi, Japan.
Hazeki
K
K
Fukui
Y
Y
Seya
T
T
Okada
T
T
Hazeki
O
O
Ui
M
M
D000730:Androstadienes / Q000494:pharmacology; D000818:Animals; D002460:Cell Line; D006168:Guinea Pigs; D006801:Humans; D066298:In Vitro Techniques; D046911:Macromolecular Substances; D009504:Neutrophils / Q000187:drug effects / Q000502:physiology*; D010587:Phagocytosis / Q000187:drug effects; D019869:Phosphatidylinositol 3-Kinases; D010739:Phospholipase D / Q000037:antagonists & inhibitors; D010748:Phosphopeptides / Q000032:analysis; D010766:Phosphorylation; D017853:Phosphotransferases (Alcohol Group Acceptor) / Q000302:isolation & purification / Q000378:metabolism*; D019000:Phosphotyrosine; D011505:Protein-Tyrosine Kinases / Q000378:metabolism; D017452:Receptors, IgG / Q000302:isolation & purification / Q000502:physiology*; D015398:Signal Transduction; D014407:Tumor Cells, Cultured; D014443:Tyrosine / Q000031:analogs & derivatives / Q000032:analysis / Q000378:metabolism; D000077191:Wortmannin
D000730:Androstadienes; D046911:Macromolecular Substances; D010748:Phosphopeptides; D017452:Receptors, IgG; D019000:Phosphotyrosine; D014443:Tyrosine; D019869:Phosphatidylinositol 3-Kinases; D017853:Phosphotransferases (Alcohol Group Acceptor); D011505:Protein-Tyrosine Kinases; D010739:Phospholipase D; D000077191:Wortmannin