Three domains of SLP-76 are required for its optimal function in a T cell line.
We and others have shown that overexpression of SLP-76 augments TCR-stimulated IL-2 promoter activity in the Jurkat T cell line. In this report we investigate the signaling mechanisms through which SLP-76 mediates its effect on T cell activation. We show that overexpressed SLP-76 acts downstream of TCR-stimulated protein tyrosine kinases, but does not affect calcium signaling. Overexpression of SLP-76 does, however, augment TCR stimulation of both ERK (extracellular signal-regulated kinase) activity and a reporter construct driven by activating protein-1 binding sites. Structure/function analysis reveals that three distinct regions of SLP-76, each important for protein associations, are required for augmentation of TCR-induced nuclear factor-AT activity. These data suggest that SLP-76 functions as an adapter molecule that requires three unique domains to link proximal TCR signals in T cells.
Musci
M A
MA
Graduate Program in Immunology, University of Iowa College of Medicine, Iowa City 52242, USA.
Motto
D G
DG
Ross
S E
SE
Fang
N
N
Koretzky
G A
GA
D048868:Adaptor Proteins, Signal Transducing; D002118:Calcium / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000502:physiology; D006801:Humans; D019169:Jurkat Cells; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D050778:NFATC Transcription Factors; D009419:Nerve Tissue Proteins / Q000378:metabolism; D009687:Nuclear Proteins; D010750:Phosphoproteins / Q000737:chemistry / Q000502:physiology*; D011948:Receptors, Antigen, T-Cell / Q000502:physiology; D018808:Transcription Factor AP-1 / Q000378:metabolism; D014157:Transcription Factors / Q000502:physiology
D048868:Adaptor Proteins, Signal Transducing; D004268:DNA-Binding Proteins; D050778:NFATC Transcription Factors; D009419:Nerve Tissue Proteins; D009687:Nuclear Proteins; D010750:Phosphoproteins; D011948:Receptors, Antigen, T-Cell; C092947:SLP-76 signal Transducing adaptor proteins; D018808:Transcription Factor AP-1; D014157:Transcription Factors; D020928:Mitogen-Activated Protein Kinases; D002118:Calcium