Adaptor function for the Syk kinases interacting protein 3BP2 in IL-2 geneactivation

Syk-family tyrosine kinases are essential for lymphocyte development and ac tivation. Using a yeast two-hybrid screen to identify Syk kinases-interacti ng proteins (SKIPs), we isolated 3BP2, an Abl SHE-interacting protein of un known function. 3BP2 was selectively expressed in hematopoietic/lymphoid ti ssues and bound via its SH2 domain activated Syk-family kinases in mammalia n cells, including in antigen receptor-stimulated T cells. In addition to Z ap-70, the 3BP2 SH2 domain associated in vitro with LAT, Grb2, PLC gamma 1, and Cbl from activated T cell lysates. Transient 3BP2 overexpression induc ed transcriptional activation of the IL-2 promoter and its NFAT or AP-1 ele ments. This activity was dependent on the SH2 and pleckstrin-homology domai ns 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 L AT-containing signaling complex involved in TCR-mediated gene transcription .