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.
Mesh Terms:
Animals, COS Cells, DNA-Binding Proteins, Enzyme Precursors, Gene Expression Regulation, Humans, Interleukin-2, Intracellular Signaling Peptides and Proteins, Jurkat Cells, Lymphocyte Activation, NFATC Transcription Factors, Nuclear Proteins, Promoter Regions, Genetic, Protein-Tyrosine Kinases, Proto-Oncogene Proteins c-abl, Saccharomyces cerevisiae, Signal Transduction, T-Lymphocytes, Tissue Distribution, Transcription Factor AP-1, Transcription Factors, Transcriptional Activation, ZAP-70 Protein-Tyrosine Kinase, src Homology Domains
Immunity
Date: Nov. 01, 1998
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