Association of tissue factor with a gamma chain homodimer of the IgE receptor type I in cultured human monocytes.
Tissue factor (TF) is a high-affinity receptor for coagulation factors VII (F VII) and VIIa. The F VII/VIIa/TF complex is the major cellular initiator of the extrinsic coagulation cascade. We found that the occupancy of TF by its ligand, F VIIa, is involved with signal transduction and that TF is associated with the gamma chain homodimer identified as a component of IgE receptor type I (Fc epsilon RI). When 4-day cultured human monocytes were incubated with F VIIa, several polypeptides, especially a 70-kDa polypeptide, were transiently phosphorylated on tyrosine, residues. These phosphorylation events were inhibited by prior binding of anti-TF monoclonal antibody (mAb) HTF-K14, but not anti-TF mAb HTF-K180 to intact cultured monocytes. HTF-K14 blocked the binding of F VII/ VIIa to cell surface TF, whereas HTF-K180 did not. Anti-TF immunoprecipitates prepared from 1% digitonin lysates of cultured human monocytes incorporated phosphate in a gamma chain homodimer when incubated with [gamma-32P] ATP. The identity of the T-associated structures as gamma chains was established by immunoblot analysis of anti-TF mAb immunoprecipitates with anti-gamma chain mAb. In addition, anti-TF immunoblot analysis showed that TF co-precipitated with anti-gamma chain mAb. Our data suggest that gamma chains may play an important role in signaling via TF in human monocytes/macrophages.
Department of Clinical Sciences and Laboratory Medicine, Kansai Medical University, Osaka, Japan.
M
M
Masuda
S
S
Nakamura
T
T
Murakami
Y
Y
Komiyama
H
H
Takahashi
D002478:Cells, Cultured; D015942:Factor VIIa / Q000378:metabolism; D006801:Humans; D008264:Macrophages / Q000276:immunology / Q000378:metabolism; D009000:Monocytes / Q000276:immunology* / Q000378:metabolism; D010766:Phosphorylation; D019000:Phosphotyrosine / Q000378:metabolism; D011485:Protein Binding; D017455:Receptors, IgE / Q000378:metabolism*; D015398:Signal Transduction; D013925:Thromboplastin / Q000378:metabolism*
D017455:Receptors, IgE; D019000:Phosphotyrosine; D013925:Thromboplastin; D015942:Factor VIIa