Regulation of ITAM signaling by specific sequences in Ig-beta B cell antigen receptor subunit.
B cell antigen receptors (BCR) are composed of an antigen binding subunit, the membrane Ig, and Ig-alpha/Ig-beta heterodimers, that contain a transducing motif named ITAM for "immuno-receptor tyrosine-based activation motif." Ig-alpha and Ig-beta ITAMs only differ by four amino acids located before the second conserved tyrosine (DCSM in Ig-alpha and QTAT in Ig-beta), which determine the in vitro association of Ig-alpha with the src kinase fyn. We have previously shown that Ig-alpha and Ig-beta BCR subunits activate different signaling pathways by expressing, in B cells, FcgammaRII chimeras containing the cytoplasmic tails of Ig-alpha or Ig-beta. We report here that the signaling capacity of Ig-beta ITAM is regulated by peptide sequences located inside (QTAT region) or outside the ITAM (flanking sequences). Furthermore, when isolated, Ig-alpha and Ig-beta ITAM have similar abilities as the entire Ig-alpha tail and the whole BCR in triggering tyrosine kinase activation, an increase of intracellular calcium concentration as well as late events of cell activation as assessed by cytokine secretion. These data show that alterations that modify the ability of Ig-alpha and Ig-beta to interact in vitro with the src kinase fyn (switch between QTAT and DCSM) also determine signal transduction capabilities of these molecules expressed in B cells.
Cassard
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CJF 95-01, INSERM, Institut Curie, 75231 Paris cedex 05, France.
Choquet
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Fridman
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WH
Bonnerot
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C
D000595:Amino Acid Sequence; D000818:Animals; D015703:Antigens, CD / Q000502:physiology*; D001402:B-Lymphocytes / Q000502:physiology*; D051925:CD79 Antigens; D002118:Calcium / Q000502:physiology; D002460:Cell Line; D003593:Cytoplasm / Q000502:physiology; D007376:Interleukin-2 / Q000378:metabolism; D051379:Mice; D008969:Molecular Sequence Data; D011947:Receptors, Antigen, B-Cell / Q000502:physiology*; D017452:Receptors, IgG / Q000502:physiology; D011993:Recombinant Fusion Proteins; D015398:Signal Transduction; D014443:Tyrosine / Q000502:physiology
D015703:Antigens, CD; D051925:CD79 Antigens; C497882:Cd79a protein, mouse; C497884:Cd79b protein, mouse; D007376:Interleukin-2; D011947:Receptors, Antigen, B-Cell; D017452:Receptors, IgG; D011993:Recombinant Fusion Proteins; D014443:Tyrosine; D002118:Calcium