Identification of novel cytoplasmic factors responsible for cell growth and death.

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The ability of B cells to respond to antigen relies on signals transmitted through the B cell antigen receptor (BCR) complex. Activation of cytoplasmic protein tyrosine kinases (PTKs) is the earliest measurable biochemical response to BCR cross-linking. The initial event leads to the generation of secondary signals including Ras activation, phosphatidylinositol 3-kinase (PI-3K) activation, phospholipase C (PLC)-γ2 activation.Based upon our previous evidence that Syk, a BCR-associated PTK, is essential for PLC-γ2 activation, we purified tyrosine-phosphorylated proteins mediated by Syk. Among 15 purified proteins, two molecules (BLNK and BCAP) were turned out to play an important role in BCR-mediated apoptosis. In fact, BLNK-deficient B cells abolished apoptosis, whereas this BCR-mediated apoptosis was enhanced by loss of BCAP.