Association of tissue factor with a γ chain homodimer of the IgE receptor type I in cultured human monocytes

Abstract

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 γ chain homodimer identified as a component of IgE receptor type I (FcϵRI). 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 FVII/Vila 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 γ chain homodimer when incubated with [γ‐³²P] ATP. The identity of the TF‐associated structures as γ chains was established by immunoblot analysis of anti‐TF mAb immunoprecipitates with anti‐γ chain mAb. In addition, anti‐TF immunoblot analysis showed that TF co‐precipitated with anti‐γ chain mAb. Our data suggest that γ chains may play an important role in signaling via TF in human monocytes/macrophages.