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http://purl.uniprot.org/citations/9601638http://www.w3.org/1999/02/22-rdf-syntax-ns#typehttp://purl.uniprot.org/core/Journal_Citation
http://purl.uniprot.org/citations/9601638http://www.w3.org/1999/02/22-rdf-syntax-ns#typehttp://purl.uniprot.org/core/Journal_Citation
http://purl.uniprot.org/citations/9601638http://www.w3.org/2000/01/rdf-schema#comment"

Background

To elucidate the role of the Src family kinase Lyn in B cell receptor (BCR) signaling, we and others previously generated lyn-/-mice and analyzed their B cell responses. Although the initiation of BCR signaling in lyn-/-B cells is delayed, BCR-induced ERK2 activation and proliferation are enhanced. As the co-receptors Fc gamma RIIb1 and CD22 have been shown to be negative regulators of BCR signaling, we have now examined their functional roles in lyn-/- B cells.

Results

B cells from lyn-/-mice have increased expression of the protein product of the early response gene egr-1, enhanced activation of Jun N-terminal kinase (JNK), and elevated calcium responses upon BCR cross-linking. Tyrosine phosphorylation of Fc gamma RIIb1 in lyn-/-B cells was reduced but negative regulation of the BCR signal by Fc gamma RIIb1 was only modestly impaired. In contrast, tyrosine phosphorylation of CD22 was greatly decreased in lyn-/-B cells, correlating with the inability of CD22 to downregulate the BCR-induced calcium response in these cells. Surprisingly, CD22 remains capable of regulating the ERK2 and JNK pathways in lyn-/-B cells, which may relate to the small residual increase in BCR-induced CD22 phosphorylation.

Conclusions

BCR signal initiation and negative regulation by Fc gamma RIIb1 is not critically dependent on Lyn. In contrast, Lyn plays a particularly important role in the tyrosine phosphorylation of CD22 and in the consequent inhibition of BCR-induced calcium influx. The net result of the Lyn deficiency in B cells is hyperresponsiveness to antigen stimulation, which may explain the autoimmunity observed in lyn-/- mice."xsd:string
http://purl.uniprot.org/citations/9601638http://purl.org/dc/terms/identifier"doi:10.1016/s0960-9822(98)70223-4"xsd:string
http://purl.uniprot.org/citations/9601638http://purl.org/dc/terms/identifier"doi:10.1016/s0960-9822(98)70223-4"xsd:string
http://purl.uniprot.org/citations/9601638http://purl.uniprot.org/core/author"Lowell C.A."xsd:string
http://purl.uniprot.org/citations/9601638http://purl.uniprot.org/core/author"Lowell C.A."xsd:string
http://purl.uniprot.org/citations/9601638http://purl.uniprot.org/core/author"Chan V.W."xsd:string
http://purl.uniprot.org/citations/9601638http://purl.uniprot.org/core/author"Chan V.W."xsd:string
http://purl.uniprot.org/citations/9601638http://purl.uniprot.org/core/author"DeFranco A.L."xsd:string
http://purl.uniprot.org/citations/9601638http://purl.uniprot.org/core/author"DeFranco A.L."xsd:string
http://purl.uniprot.org/citations/9601638http://purl.uniprot.org/core/date"1998"xsd:gYear
http://purl.uniprot.org/citations/9601638http://purl.uniprot.org/core/date"1998"xsd:gYear
http://purl.uniprot.org/citations/9601638http://purl.uniprot.org/core/name"Curr. Biol."xsd:string
http://purl.uniprot.org/citations/9601638http://purl.uniprot.org/core/name"Curr. Biol."xsd:string
http://purl.uniprot.org/citations/9601638http://purl.uniprot.org/core/pages"545-553"xsd:string
http://purl.uniprot.org/citations/9601638http://purl.uniprot.org/core/pages"545-553"xsd:string
http://purl.uniprot.org/citations/9601638http://purl.uniprot.org/core/title"Defective negative regulation of antigen receptor signaling in Lyn-deficient B lymphocytes."xsd:string
http://purl.uniprot.org/citations/9601638http://purl.uniprot.org/core/title"Defective negative regulation of antigen receptor signaling in Lyn-deficient B lymphocytes."xsd:string
http://purl.uniprot.org/citations/9601638http://purl.uniprot.org/core/volume"8"xsd:string
http://purl.uniprot.org/citations/9601638http://purl.uniprot.org/core/volume"8"xsd:string
http://purl.uniprot.org/citations/9601638http://www.w3.org/2004/02/skos/core#exactMatchhttp://purl.uniprot.org/pubmed/9601638
http://purl.uniprot.org/citations/9601638http://www.w3.org/2004/02/skos/core#exactMatchhttp://purl.uniprot.org/pubmed/9601638
http://purl.uniprot.org/citations/9601638http://xmlns.com/foaf/0.1/primaryTopicOfhttps://pubmed.ncbi.nlm.nih.gov/9601638
http://purl.uniprot.org/citations/9601638http://xmlns.com/foaf/0.1/primaryTopicOfhttps://pubmed.ncbi.nlm.nih.gov/9601638
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