Tyrosine phosphorylation of she is mediated through lyn and syk in B cell receptor signaling

Abstract

She protein is tyrosine phosphorylated upon B cell receptor (BCR) activation and after its phosphorylation interacts with the adaptor protein Grb2. In turn, Grb2 interacts with the guanine nucleotide exchange factor for Ras, mSOS. Several protein-tyrosine kinases (PTKs) participate in BCR signaling. However, it is not clear which PTK is involved in the phosphorylation of She, resulting in coupling to the Ras pathway. Tyrosine phosphorylation of She and its association with Grb2 were profoundly reduced in both Lyn- and Syk-deficient B cells upon BCR stimulation. Furthermore, kinase activity of these PTKs was required for phosphorylation of She. She interacted with Syk in B cells. This interaction and the requirement of Syk kinase activity for phosphorylation of She were also demonstrated by cotransfection in COS cells. Because Lyn is required for activation of Syk upon receptor stimulation, our results suggest that the Lyn-activated Syk phosphorylates She during BCR signaling.