PROTEIN-TYROSINE KINASE ACTIVATION PROVIDES AN EARLY AND OBLIGATORY SIGNAL IN ANTI-FRP-1 CD98/4F2 MONOCLONAL-ANTIBODY INDUCED CELL-FUSION MEDIATED BY HIV GP160/

The mechanism by which anti-fusion regulatory protein-1 (FRP-1) monocl onal antibody (mAb) induced cell fusion was investigated using U2ME-7 cells that are CD4(+)U937 cells transfected with the HIV gp160 gene. P rotein kinase inhibitors (H-7, H-89, herbimycin A and genistein) suppr essed cell fusion of Cd(+)U2ME-7 cells induced by anti-FRP-1 mAb. H-7 and H-89 also inhibited the cell aggregation, but herbimycin A and gen istein did not. Intriguingly, only when herbimycin A was added either before or simultaneously with addition of anti-FRP-1 mAb, was cell fus ion suppressed, suggesting that tyrosine kinase is related with the in itial step of polykaryocyte formation. Anti-FRP-1 mAb induced the rapi d tyrosine phosphorylation of multiple cellular proteins. These effect s occurred within 1 min and returned to near baseline by 60 min. The r apid tyrosine phosphorylation was suppressed by herbimycin A and genis tein. Although it remains to be determined which protein tyrosine kina se(s) is involved in this response, pp130 tyrosine phosphorylation app ears to be a specific and early signal transmitted after the interacti on of FRP-1 with a specific antibody. pp130 was present in the cytosol fraction and was distinct from pp125(FAK), p130(CAS), vinculin, and b eta 1-integrin. Thus, our study may present evidence for a novel pathw ay of protein tyrosine kinases that phosphorylate specific, still unkn own protein substrates during polykaryocyte formation.