Association of SLP-65/BLNK with the B cell antigen receptor through a non-ITAM tyrosine of Ig-alpha.
The cytoplasmic adaptor protein SLP-65 (BLNK or BASH) is a critical downstream effector of the B cell antigen receptor (BCR). Tyrosine-phosphorylated SLP-65 assembles intracellular signaling complexes such as the Ca(2 +) initiation complex encompassing phospholipase C-gamma2 and Bruton's tyrosine kinase. It is, however, unclear how the SLP-65 signaling module can be recruited to the plasma membrane. Here we show that following B cell stimulation, SLP-65 associates directly with the BCR signaling subunit, the Ig-alpha / Ig-beta heterodimer. The interaction is mediated by the Src homology 2 domain of SLP-65 and the phosphorylated Ig-alpha tyrosine 204, which is located outside of the immunoreceptor tyrosine-based activation motif. Our data identify an unexpected BCR phosphorylation pattern and indicate that Ig-alpha has the capability to serve as transmembrane adaptor in BCR signaling.
Engels
N
N
Institute of Biology III, University of Freiburg and Max Planck Institute of Immunobiology, Freiburg, Germany.
Wollscheid
B
B
Wienands
J
J
D048868:Adaptor Proteins, Signal Transducing; D020816:Amino Acid Motifs; D000595:Amino Acid Sequence; D000818:Animals; D015703:Antigens, CD / Q000737:chemistry* / Q000378:metabolism*; D001402:B-Lymphocytes / Q000276:immunology*; D051925:CD79 Antigens; D002352:Carrier Proteins / Q000737:chemistry / Q000378:metabolism*; D002460:Cell Line; D018448:Models, Immunological; D008969:Molecular Sequence Data; D010750:Phosphoproteins / Q000737:chemistry / Q000378:metabolism*; D010766:Phosphorylation; D019000:Phosphotyrosine / Q000378:metabolism; D011947:Receptors, Antigen, B-Cell / Q000737:chemistry* / Q000378:metabolism*; D016415:Sequence Alignment; D018909:src Homology Domains
D048868:Adaptor Proteins, Signal Transducing; D015703:Antigens, CD; C113939:B cell linker protein; D051925:CD79 Antigens; D002352:Carrier Proteins; D010750:Phosphoproteins; D011947:Receptors, Antigen, B-Cell; D019000:Phosphotyrosine