The serine and threonine residues in the Ig-alpha cytoplasmic tail negatively regulate immunoreceptor tyrosine-based activation motif-mediated signaltransduction

The B cell antigen receptor (BCR) is a multiprotein complex consisting of t he membrane-bound Ig molecule and the Ig-alpha/Ig-beta heterodimer. On BCR engagement, Ig-alpha and Ig-beta become phosphorylated not only on tyrosine residues of the immunoreceptor tyrosine-based activation motif but also on serine and threonine residues. We have mutated all serine and threonine re sidues in the Ig-alpha tail to alanine and valine. respectively. The mutate d Ig-alpha sequence was expressed either as a single-chain Fv/Ig-alpha mole cule or in the context of the complete BCR. In both cases, the mutated Ig-a lpha showed a stronger tyrosine phosphorylation than the wild type Ig-alpha and initiated increased signaling on stimulation. These findings suggest t hat serine/threonine kinases can negatively regulate signal transduction fr om the BCR.