B and T lymphocyte attenuator regulates B cell receptor signaling by targeting Syk and BLNK.

摘要: B and T lymphocyte attenuator (BTLA) functions as a negative regulator of cell activation proliferation. Although the role BTLA in regulating responses has been characterized, thorough investigation into precise molecular mechanisms involved BTLA-mediated attenuation and, more specifically, its not presented. In this study, we have begun to elucidate biochemical by which inhibit activation. We describe surface expression on various human subsets confirm ability attenuate proliferation upon associating with known ligand, herpesvirus entry mediator (HVEM). associates BCR binding HVEM, recruits tyrosine phosphatase Src homology 2 domain-containing 1 reduces signaling molecules downstream BCR. This is exemplified quantifiable decrease phosphorylation protein kinase Syk, measured absolute quantification mass spectrometry. Furthermore, effector signaling, including linker protein, phospholipase Cgamma2, NF-kappaB, display decreased nuclear translocation, respectively, after HVEM. These results begin provide insight mechanism negatively regulates indicates that an inhibitory coreceptor pathway attenuates targeting Syk protein.