FcgammaRI activation of phospholipase Cgamma1 and protein kinase C in dibutyryl cAMP-differentiated U937 cells is dependent solely on the tyrosine-kinase activated form of phosphatidylinositol-3-kinase.
The human high affinity receptor for immunoglobulin G, FcgammaRI, in dibutyryl cyclic AMP (dbcAMP)-differentiated U937 cells, is coupled to the activation of phospholipase C (PLC) and the conventional protein kinase C (PKC) isoforms, alpha, beta, and gamma. Here we demonstrate that aggregation of FcgammaRI activates the tyrosine-kinase regulated form of phosphatidylinositol-3-kinase (PI-3-kinase) and that an increase of phosphatidylinositol trisphosphate (PIP3) is essential for the activation and translocation of PLCgamma1 in these cells. In addition, activation of the PKC isoforms was ablated by specific inhibitors of PI3-kinase or by overexpression of a dominant negative p85 subunit of PI3-kinase. The findings reported here demonstrate that PLCgamma1 and PKC activation by FcgammaRI are downstream of PI3-kinase, and that in contrast to cytokine primed cells, only the tyrosine-kinase activated isoform of PI3-kinase is coupled to FcgammaRI in dbcAMP-differentiated cells.
Melendez
A J
AJ
Department of Medicine and Therapeutics and Division of Biochemistry and Molecular Biology, University of Glasgow, Glasgow, UK.
Harnett
M M
MM
Allen
J M
JM
D003994:Bucladesine / Q000494:pharmacology; D002454:Cell Differentiation; D004789:Enzyme Activation; D006801:Humans; D007527:Isoenzymes / Q000378:metabolism*; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism*; D011493:Protein Kinase C / Q000378:metabolism*; D011505:Protein-Tyrosine Kinases / Q000378:metabolism; D011940:Receptor Aggregation; D020239:Receptor Cross-Talk; D017452:Receptors, IgG / Q000378:metabolism*; D015398:Signal Transduction; D010738:Type C Phospholipases / Q000378:metabolism*; D020298:U937 Cells
D007527:Isoenzymes; D017452:Receptors, IgG; D003994:Bucladesine; D019869:Phosphatidylinositol 3-Kinases; D011505:Protein-Tyrosine Kinases; D011493:Protein Kinase C; D010738:Type C Phospholipases