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rdf:type |
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lifeskim:mentions |
umls-concept:C0033681,
umls-concept:C0034789,
umls-concept:C0044602,
umls-concept:C0205164,
umls-concept:C1333707,
umls-concept:C1418576,
umls-concept:C1418577,
umls-concept:C1423080,
umls-concept:C1423613,
umls-concept:C1515655,
umls-concept:C1519726,
umls-concept:C1710236,
umls-concept:C1711351,
umls-concept:C1948023
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pubmed:issue |
6
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pubmed:dateCreated |
1996-6-19
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pubmed:abstractText |
We and others have demonstrated that the c-cbl proto-oncogene product is one of the earliest targets of tyrosine phosphorylation upon T cell receptor stimulation. Given the similarities in the B and T lymphocyte antigen receptors, and the induction of pre-B leukemias in mice by the v-cbl oncogene, we examined the potential involvement of Cbl in B cell receptor signaling. We demonstrate prominent and early tyrosine phosphorylation of Cbl upon stimulation of human B cell lines through surface IgM. Cbl was associated in vivo with Fyn and, to a lesser extent, other Src family kinases. B cell activation also induced a prominent association of Cbl with Syk tyrosine kinase. A substantial fraction of Cbl was constitutively associated with Grb2 and this interaction was mediated by Grb2 SH3 domains. Tyrosine-phosphorylated Shc, which prominently associated with Grb2, was detected in association with Cbl in activated B cells. Thus, Grb2 and Shc adaptors, which associate with immunoreceptor tyrosine based activation motifs, may link Cbl to the B cell receptor. B cell activation also induced a prominent association between Cbl and the p85 subunit of phosphatidylinositol (PI) 3-kinase resulting in the association of a substantial fraction of PI 3-kinase activity with Cbl. Thus, Cbl is likely to play an important role to couple the B cell receptor to the PI 3-kinase pathway. Our results strongly suggest a role for p120cbl in signaling downstream of the B cell receptor and support the idea that Cbl participates in a general signal transduction function downstream of the immune cell surface receptors.
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pubmed:grant |
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pubmed:language |
eng
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pubmed:journal |
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pubmed:citationSubset |
IM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Adaptor Proteins, Signal Transducing,
http://linkedlifedata.com/resource/pubmed/chemical/Enzyme Precursors,
http://linkedlifedata.com/resource/pubmed/chemical/FYN protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Fyn protein, mouse,
http://linkedlifedata.com/resource/pubmed/chemical/GRB2 Adaptor Protein,
http://linkedlifedata.com/resource/pubmed/chemical/GRB2 protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Glutathione Transferase,
http://linkedlifedata.com/resource/pubmed/chemical/Grb2 protein, mouse,
http://linkedlifedata.com/resource/pubmed/chemical/Intracellular Signaling Peptides...,
http://linkedlifedata.com/resource/pubmed/chemical/Macromolecular Substances,
http://linkedlifedata.com/resource/pubmed/chemical/Oncogene Protein v-cbl,
http://linkedlifedata.com/resource/pubmed/chemical/Phosphatidylinositol 3-Kinases,
http://linkedlifedata.com/resource/pubmed/chemical/Phosphotransferases (Alcohol Group...,
http://linkedlifedata.com/resource/pubmed/chemical/Protein-Tyrosine Kinases,
http://linkedlifedata.com/resource/pubmed/chemical/Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Proto-Oncogene Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Proto-Oncogene Proteins c-fyn,
http://linkedlifedata.com/resource/pubmed/chemical/Receptors, Antigen, B-Cell,
http://linkedlifedata.com/resource/pubmed/chemical/Recombinant Fusion Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Retroviridae Proteins, Oncogenic,
http://linkedlifedata.com/resource/pubmed/chemical/Syk kinase
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pubmed:status |
MEDLINE
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pubmed:month |
Feb
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pubmed:issn |
0021-9258
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pubmed:author |
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pubmed:issnType |
Print
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pubmed:day |
9
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pubmed:volume |
271
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
3187-94
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pubmed:dateRevised |
2011-11-2
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pubmed:meshHeading |
pubmed-meshheading:8621719-Adaptor Proteins, Signal Transducing,
pubmed-meshheading:8621719-Animals,
pubmed-meshheading:8621719-B-Lymphocytes,
pubmed-meshheading:8621719-Cell Line,
pubmed-meshheading:8621719-Enzyme Precursors,
pubmed-meshheading:8621719-GRB2 Adaptor Protein,
pubmed-meshheading:8621719-Glutathione Transferase,
pubmed-meshheading:8621719-Humans,
pubmed-meshheading:8621719-Intracellular Signaling Peptides and Proteins,
pubmed-meshheading:8621719-Leukemia, B-Cell,
pubmed-meshheading:8621719-Macromolecular Substances,
pubmed-meshheading:8621719-Mice,
pubmed-meshheading:8621719-Oncogene Protein v-cbl,
pubmed-meshheading:8621719-Oncogenes,
pubmed-meshheading:8621719-Phosphatidylinositol 3-Kinases,
pubmed-meshheading:8621719-Phosphorylation,
pubmed-meshheading:8621719-Phosphotransferases (Alcohol Group Acceptor),
pubmed-meshheading:8621719-Protein-Tyrosine Kinases,
pubmed-meshheading:8621719-Proteins,
pubmed-meshheading:8621719-Proto-Oncogene Proteins,
pubmed-meshheading:8621719-Proto-Oncogene Proteins c-fyn,
pubmed-meshheading:8621719-Receptors, Antigen, B-Cell,
pubmed-meshheading:8621719-Recombinant Fusion Proteins,
pubmed-meshheading:8621719-Retroviridae Proteins, Oncogenic,
pubmed-meshheading:8621719-src Homology Domains
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pubmed:year |
1996
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pubmed:articleTitle |
p120cbl is a major substrate of tyrosine phosphorylation upon B cell antigen receptor stimulation and interacts in vivo with Fyn and Syk tyrosine kinases, Grb2 and Shc adaptors, and the p85 subunit of phosphatidylinositol 3-kinase.
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pubmed:affiliation |
Lymphocyte Biology Section, Division of Rheumatology and Immunology, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts 02115, USA.
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pubmed:publicationType |
Journal Article,
Research Support, U.S. Gov't, P.H.S.,
Research Support, U.S. Gov't, Non-P.H.S.,
Research Support, Non-U.S. Gov't
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