RECONSTITUTION OF B-CELL ANTIGEN RECEPTOR-INDUCED SIGNALING EVENTS INA NONLYMPHOID CELL-LINE BY EXPRESSING THE SYK PROTEIN-TYROSINE KINASE

B cell antigen receptor (BCR) cross-linking activates both Src family and Syk tyrosine kinases, resulting in increased cellular protein-tyro sine phosphorylation and activation of several downstream signaling en zymes. To define the role of Syk in these events, we expressed the BCR in the AtT20 mouse pituitary cell line. These nonlymphoid cells endog enously expressed the Src family kinase Fyn but not Syk. Anti-IgM stim ulation of these cells failed to induce most of the signaling events t hat occur in B cells. BCR-expressing AtT20 transfectants were generate d that also expressed Syk. Syk expression reconstituted several signal ing events upon anti-IgM stimulation, including Syk phosphorylation an d association with the BCR, tyrosine phosphorylation of numerous prote ins including Shc, and activation of mitogen-activated protein kinase. In contrast, Syk expression did not reconstitute anti-IgM-induced ino sitol phosphate production. A catalytically inactive Syk mutant could associate with the BCR and become tyrosine phosphorylated but could no t reconstitute downstream signaling events. Expression of the Src fami ly kinase Lck instead of Syk also did not reconstitute signaling. Thus , wild type Syk was required to reconstitute several BCR-induced signa ling events but was not sufficient to couple the BCR to the phosphoino sitide signaling pathway.