The serine and threonine residues in the Ig-alpha cytoplasmic tail negatively regulate immunoreceptor tyrosine-based activation motif-mediated signal transduction.
The B cell antigen receptor (BCR) is a multiprotein complex consisting of the 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 residues in the Ig-alpha tail to alanine and valine, respectively. The mutated Ig-alpha sequence was expressed either as a single-chain Fv/Ig-alpha molecule or in the context of the complete BCR. In both cases, the mutated Ig-alpha showed a stronger tyrosine phosphorylation than the wild-type Ig-alpha and initiated increased signaling on stimulation. These findings suggest that serine/threonine kinases can negatively regulate signal transduction from the BCR.
Müller
R
R
Department of Molecular Immunology, Biology III, University of Freiburg and Max-Planck-Institute for Immunobiology, Stübeweg 51, 79108 Freiburg, Germany.
Wienands
J
J
Reth
M
M
D048868:Adaptor Proteins, Signal Transducing; D000595:Amino Acid Sequence; D015703:Antigens, CD / Q000235:genetics / Q000378:metabolism*; D051925:CD79 Antigens; D002352:Carrier Proteins / Q000378:metabolism; D003593:Cytoplasm / Q000378:metabolism; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006801:Humans; D007128:Immunoglobulin Fragments / Q000235:genetics / Q000378:metabolism; D007135:Immunoglobulin Variable Region / Q000235:genetics / Q000378:metabolism; D008969:Molecular Sequence Data; D010750:Phosphoproteins / Q000378:metabolism; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism*; D017027:Protein Tyrosine Phosphatases / Q000494:pharmacology; D011947:Receptors, Antigen, B-Cell / Q000235:genetics / Q000378:metabolism*; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism; D012694:Serine / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction; D013912:Threonine / Q000235:genetics / Q000378:metabolism*; D014407:Tumor Cells, Cultured; D014443:Tyrosine / Q000378:metabolism*; D014638:Vanadates / Q000494:pharmacology
D048868:Adaptor Proteins, Signal Transducing; D015703:Antigens, CD; C113939:B cell linker protein; D051925:CD79 Antigens; C497881:CD79A protein, human; D002352:Carrier Proteins; D004791:Enzyme Inhibitors; D007128:Immunoglobulin Fragments; D007135:Immunoglobulin Variable Region; D010750:Phosphoproteins; D011947:Receptors, Antigen, B-Cell; D011993:Recombinant Fusion Proteins; C055966:immunoglobulin Fv; C076715:pervanadate; D013912:Threonine; D014638:Vanadates; D014443:Tyrosine; D012694:Serine; D017346:Protein Serine-Threonine Kinases; D017027:Protein Tyrosine Phosphatases