Linked Life Data

19155498

Source:http://linkedlifedata.com/resource/pubmed/id/19155498

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
3
pubmed:dateCreated
2009-1-21
pubmed:abstractText
B and T lymphocyte attenuator (BTLA) functions as a negative regulator of T cell activation and proliferation. Although the role of BTLA in regulating T cell responses has been characterized, a thorough investigation into the precise molecular mechanisms involved in BTLA-mediated lymphocyte attenuation and, more specifically, its role in regulating B cell activation has not been presented. In this study, we have begun to elucidate the biochemical mechanisms by which BTLA functions to inhibit B cell activation. We describe the cell surface expression of BTLA on various human B cell subsets and confirm its ability to attenuate B cell proliferation upon associating with its known ligand, herpesvirus entry mediator (HVEM). BTLA associates with the BCR and, upon binding to HVEM, recruits the tyrosine phosphatase Src homology 2 domain-containing phosphatase 1 and reduces activation of signaling molecules downstream of the BCR. This is exemplified by a quantifiable decrease in tyrosine phosphorylation of the protein tyrosine kinase Syk, as measured by absolute quantification mass spectrometry. Furthermore, effector molecules downstream of BCR signaling, including the B cell linker protein, phospholipase Cgamma2, and NF-kappaB, display decreased activation and nuclear translocation, respectively, after BTLA activation by HVEM. These results begin to provide insight into the mechanism by which BTLA negatively regulates B cell activation and indicates that BTLA is an inhibitory coreceptor of the BCR signaling pathway and attenuates B cell activation by targeting the downstream signaling molecules Syk and B cell linker protein.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
AIM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Feb
pubmed:issn
1550-6606
pubmed:author
pubmed:issnType
Electronic
pubmed:day
1
pubmed:volume
182
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
1509-17
pubmed:dateRevised
2011-11-2
pubmed:meshHeading
pubmed-meshheading:19155498-Adaptor Proteins, Signal Transducing, pubmed-meshheading:19155498-Amino Acid Sequence, pubmed-meshheading:19155498-B-Lymphocyte Subsets, pubmed-meshheading:19155498-Cell Line, Tumor, pubmed-meshheading:19155498-Cell Nucleus, pubmed-meshheading:19155498-Down-Regulation, pubmed-meshheading:19155498-Humans, pubmed-meshheading:19155498-Intracellular Signaling Peptides and Proteins, pubmed-meshheading:19155498-Lymphocyte Activation, pubmed-meshheading:19155498-Molecular Sequence Data, pubmed-meshheading:19155498-NF-kappa B, pubmed-meshheading:19155498-Phosphorylation, pubmed-meshheading:19155498-Protein-Tyrosine Kinases, pubmed-meshheading:19155498-Receptors, Antigen, B-Cell, pubmed-meshheading:19155498-Receptors, Immunologic, pubmed-meshheading:19155498-Signal Transduction
pubmed:year
2009
pubmed:articleTitle
B and T lymphocyte attenuator regulates B cell receptor signaling by targeting Syk and BLNK.
pubmed:affiliation
Department of Protein Chemistry, Genentech, Inc., South San Francisco, CA 94080, USA.
pubmed:publicationType
Journal Article