Adaptor function for the Syk kinases-interacting protein 3BP2 in IL-2 gene activation.
Syk-family tyrosine kinases are essential for lymphocyte development and activation. Using a yeast two-hybrid screen to identify Syk kinases-interacting proteins (SKIPs), we isolated 3BP2, an Abl SH3-interacting protein of unknown function. 3BP2 was selectively expressed in hematopoietic/lymphoid tissues and bound via its SH2 domain activated Syk-family kinases in mammalian cells, including in antigen receptor-stimulated T cells. In addition to Zap-70, the 3BP2 SH2 domain associated in vitro with LAT, Grb2, PLCgamma1, and Cbl from activated T cell lysates. Transient 3BP2 overexpression induced transcriptional activation of the IL-2 promoter and its NFAT or AP-1 elements. This activity was dependent on the SH2 and pleckstrin-homology domains of 3BP2, and required functional Syk kinases, Ras, and calcineurin. Thus, 3BP2 is an important adaptor that may couple activated Zap-70/Syk to a LAT-containing signaling complex involved in TCR-mediated gene transcription.
Deckert
M
M
Division of Cell Biology, La Jolla Institute for Allergy and Immunology, San Diego, California 92121, USA.
Tartare-Deckert
S
S
Hernandez
J
J
Rottapel
R
R
Altman
A
A
D000818:Animals; D019556:COS Cells; D004268:DNA-Binding Proteins / Q000502:physiology; D004792:Enzyme Precursors / Q000378:metabolism / Q000502:physiology*; D005786:Gene Expression Regulation / Q000502:physiology*; D006801:Humans; D007376:Interleukin-2 / Q000096:biosynthesis* / Q000235:genetics; D047908:Intracellular Signaling Peptides and Proteins; D019169:Jurkat Cells; D008213:Lymphocyte Activation / Q000502:physiology; D050778:NFATC Transcription Factors; D009687:Nuclear Proteins; D011401:Promoter Regions, Genetic / Q000502:physiology; D011505:Protein-Tyrosine Kinases / Q000378:metabolism / Q000502:physiology*; D016315:Proto-Oncogene Proteins c-abl / Q000302:isolation & purification / Q000378:metabolism / Q000502:physiology*; D012441:Saccharomyces cerevisiae; D015398:Signal Transduction / Q000502:physiology; D000072377:Syk Kinase; D013601:T-Lymphocytes / Q000502:physiology; D014018:Tissue Distribution; D018808:Transcription Factor AP-1 / Q000502:physiology; D014157:Transcription Factors / Q000502:physiology; D015533:Transcriptional Activation; D051746:ZAP-70 Protein-Tyrosine Kinase; D018909:src Homology Domains / Q000502:physiology
D004268:DNA-Binding Proteins; D004792:Enzyme Precursors; D007376:Interleukin-2; D047908:Intracellular Signaling Peptides and Proteins; D050778:NFATC Transcription Factors; D009687:Nuclear Proteins; D018808:Transcription Factor AP-1; D014157:Transcription Factors; D011505:Protein-Tyrosine Kinases; D016315:Proto-Oncogene Proteins c-abl; C000606896:SYK protein, human; D000072377:Syk Kinase; D051746:ZAP-70 Protein-Tyrosine Kinase; C497261:ZAP70 protein, human