Role of protein tyrosine phosphorylation in monokine induction by the staphylococcal superantigen toxic shock syndrome toxin-1.
The staphylococcal superantigen toxic shock syndrome toxin-1 (TSST-1) is a potent inducer of IL-1 beta and TNF-alpha synthesis in human monocytes. As superantigens are high affinity ligands for MHC class II molecules, the induction of monokines by TSST-1 provides a biologically relevant model of MHC class II-mediated transmembrane signaling. In this study, we show that TSST-1 induces cytoplasmic protein tyrosine phosphorylation in the human monocytic cell line THP-1. This induction was greatly enhanced by cross-linking TSST-1 with biotin-avidin. The functional relevance of tyrosine phosphorylation induced by TSST-1 was demonstrated by the finding that three specific inhibitors of protein tyrosine kinases strongly inhibited the induction of IL-1 beta mRNA by TSST-1. These data suggest that protein tyrosine kinase activation plays a critical role in MHC class II-mediated transmembrane signalling by staphylococcal superantigens.
Scholl
P R
PR
Department of Medicine, Children's Hospital, Boston, MA 02115.
Trede
N
N
Chatila
T A
TA
Geha
R S
RS
D000942:Antigens, Bacterial / Q000276:immunology*; D001427:Bacterial Toxins; D002460:Cell Line; D002478:Cells, Cultured; D004768:Enterotoxins / Q000276:immunology*; D000949:Histocompatibility Antigens Class II / Q000502:physiology; D006801:Humans; D007375:Interleukin-1 / Q000235:genetics; D015846:Monokines / Q000235:genetics*; D010766:Phosphorylation; D011493:Protein Kinase C / Q000502:physiology; D011505:Protein-Tyrosine Kinases / Q000502:physiology*; D012333:RNA, Messenger / Q000032:analysis; D013210:Staphylococcus / Q000276:immunology*; D018089:Superantigens; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics; D014443:Tyrosine / Q000378:metabolism*
D000942:Antigens, Bacterial; D001427:Bacterial Toxins; D004768:Enterotoxins; D000949:Histocompatibility Antigens Class II; D007375:Interleukin-1; D015846:Monokines; D012333:RNA, Messenger; D018089:Superantigens; D014409:Tumor Necrosis Factor-alpha; C030107:enterotoxin F, Staphylococcal; D014443:Tyrosine; D011505:Protein-Tyrosine Kinases; D011493:Protein Kinase C