Hematopoietic cell-specific adapter proteins, SLP-76 and BLNK, effectively activate NF-AT as well as NF-kappaB by Syk and Tec PTKs in non-lymphoid cell lines.
To investigate the roles of various hematopoietic cell-specific adapter proteins in T cell receptor (TCR)-signaling leading to nuclear factor of activated T cell (NF-AT) and nuclear factor of kappaB (NF-kappaB) activation, we reconstituted TCR-signaling with CD8/zeta, various protein tyrosine kinases (PTKs), and adapter proteins in a non-lymphoid cell line, 293T. We show that SLP-76 and BLNK, but not LAT, effectively co-operated with Syk and Tec family PTKs to activate NF-AT and NF-kappaB. We also show that Tec family PTKs enhanced endogenous phospholipase C (PLC)-gamma1 phosphorylation induced by CD8/zeta and Syk in 293T cells. These results imply that PLC-gamma1 may play a critical role in a hematopoietic cell-specific adapter protein-mediated NF-AT and NF-kappaB activation in a non-lymphoid cell.
Department of Immunology, Faculty of Medicine, Toyama Medical and Pharmaceutical University, Sugitani, Toyama, Japan.
T
T
Yamamoto
T
T
Matsuda
A
A
Junicho
H
H
Kishi
A
A
Yoshimura
A
A
Muraguchi
D048868:Adaptor Proteins, Signal Transducing; D000077329:Agammaglobulinaemia Tyrosine Kinase; D000818:Animals; D016827:CD8 Antigens / Q000235:genetics / Q000378:metabolism; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism*; D002460:Cell Line; D004268:DNA-Binding Proteins / Q000378:metabolism*; D004792:Enzyme Precursors / Q000378:metabolism; D006412:Hematopoietic Stem Cells / Q000166:cytology / Q000276:immunology / Q000378:metabolism*; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins; D007527:Isoenzymes / Q000378:metabolism; D008565:Membrane Proteins; D016328:NF-kappa B / Q000378:metabolism*; D050778:NFATC Transcription Factors; D009687:Nuclear Proteins; D051966:Phospholipase C gamma; D010750:Phosphoproteins / Q000235:genetics / Q000378:metabolism*; D010766:Phosphorylation; D020033:Protein Isoforms / Q000235:genetics / Q000378:metabolism; D011505:Protein-Tyrosine Kinases / Q000378:metabolism; D051381:Rats; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction / Q000276:immunology; D000072377:Syk Kinase; D014157:Transcription Factors / Q000378:metabolism*; D010738:Type C Phospholipases / Q000378:metabolism; D014443:Tyrosine / Q000378:metabolism
D048868:Adaptor Proteins, Signal Transducing; C113939:B cell linker protein; D016827:CD8 Antigens; D002352:Carrier Proteins; D004268:DNA-Binding Proteins; D004792:Enzyme Precursors; D047908:Intracellular Signaling Peptides and Proteins; D007527:Isoenzymes; C110810:LAT protein, human; D008565:Membrane Proteins; D016328:NF-kappa B; D050778:NFATC Transcription Factors; D009687:Nuclear Proteins; D010750:Phosphoproteins; D020033:Protein Isoforms; D011993:Recombinant Fusion Proteins; C092947:SLP-76 signal Transducing adaptor proteins; D014157:Transcription Factors; D014443:Tyrosine; C089848:Tec protein-tyrosine kinase; D011505:Protein-Tyrosine Kinases; D000077329:Agammaglobulinaemia Tyrosine Kinase; C000606896:SYK protein, human; D000072377:Syk Kinase; C000606898:Syk protein, rat; D010738:Type C Phospholipases; D051966:Phospholipase C gamma