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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
6
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pubmed:dateCreated |
1999-10-4
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pubmed:abstractText |
Cross-linking the B cell Ag receptor (BCR) to surface Fc receptors for IgG (Fc gamma R) inhibits G1-to-S progression; the mechanism by which this occurs is not completely known. We investigated the regulation of three key cell cycle regulatory components by BCR-Fc gamma R co-cross-linking: G1-cyclins, cyclin-dependent kinases (Cdks), and the retinoblastoma gene product (Rb). Rb functions to suppress G1-to-S progression in mammalian cells. Rb undergoes cell-cycle-dependent phosphorylation, leading to its inactivation and thereby promoting S phase entry. We demonstrate in this paper for the first time that BCR-induced Rb phosphorylation is abrogated by co-cross-linking with Fc gamma R. The activation of Cdk4/6- and Cdk2-dependent Rb protein kinases is concomitantly blocked. Fc gamma R-mediated inhibition of Cdk2 activity results in part from an apparent failure to express Cdk2 protein. By contrast, inhibition of Cdk4/6 activities is not due to suppression of Cdk4/6 or cyclins D2/D3 expression or inhibition of Cdk-activating kinase activity. Cdk4- and Cdk6-immune complexes recovered from B cells following BCR-Fc gamma R co-cross-linking are devoid of coprecipitated D-type cyclins, indicating that inhibition of their Rb protein kinase activities is due in part to the absence of bound D-type cyclin. Thus, BCR-derived activation signals that up-regulate D-type cyclin and Cdk4/6 protein expression remain intact; however, Fc gamma R-mediated signals block cyclin D-Cdk4/6 assembly or stabilization. These results suggest that assembly or stabilization of D-type cyclin holoenzyme complexes 1) is an important step in the activation of Cdk4/6 by BCR signals, and 2) suffice in providing a mechanism to account for inhibition of BCR-stimulated Rb protein phosphorylation by Fc gamma R.
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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 |
AIM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Antibodies, Anti-Idiotypic,
http://linkedlifedata.com/resource/pubmed/chemical/CDC2-CDC28 Kinases,
http://linkedlifedata.com/resource/pubmed/chemical/Cdk2 protein, mouse,
http://linkedlifedata.com/resource/pubmed/chemical/Cdk4 protein, mouse,
http://linkedlifedata.com/resource/pubmed/chemical/Cdk6 protein, mouse,
http://linkedlifedata.com/resource/pubmed/chemical/Cdk9 protein, mouse,
http://linkedlifedata.com/resource/pubmed/chemical/Cdkn1b protein, mouse,
http://linkedlifedata.com/resource/pubmed/chemical/Cell Cycle Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Cyclin D,
http://linkedlifedata.com/resource/pubmed/chemical/Cyclin E,
http://linkedlifedata.com/resource/pubmed/chemical/Cyclin-Dependent Kinase 2,
http://linkedlifedata.com/resource/pubmed/chemical/Cyclin-Dependent Kinase 4,
http://linkedlifedata.com/resource/pubmed/chemical/Cyclin-Dependent Kinase 6,
http://linkedlifedata.com/resource/pubmed/chemical/Cyclin-Dependent Kinase 9,
http://linkedlifedata.com/resource/pubmed/chemical/Cyclin-Dependent Kinase Inhibitor...,
http://linkedlifedata.com/resource/pubmed/chemical/Cyclin-Dependent Kinases,
http://linkedlifedata.com/resource/pubmed/chemical/Cyclins,
http://linkedlifedata.com/resource/pubmed/chemical/DNA,
http://linkedlifedata.com/resource/pubmed/chemical/Holoenzymes,
http://linkedlifedata.com/resource/pubmed/chemical/Immunoglobulin Fab Fragments,
http://linkedlifedata.com/resource/pubmed/chemical/Microtubule-Associated Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Protein-Serine-Threonine Kinases,
http://linkedlifedata.com/resource/pubmed/chemical/Proto-Oncogene Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/RNA,
http://linkedlifedata.com/resource/pubmed/chemical/Receptors, Antigen, B-Cell,
http://linkedlifedata.com/resource/pubmed/chemical/Receptors, IgG,
http://linkedlifedata.com/resource/pubmed/chemical/Retinoblastoma Protein,
http://linkedlifedata.com/resource/pubmed/chemical/Tumor Suppressor Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/cyclin-dependent kinase-activating...
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pubmed:status |
MEDLINE
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pubmed:month |
Sep
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pubmed:issn |
0022-1767
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pubmed:author |
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pubmed:issnType |
Print
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pubmed:day |
15
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pubmed:volume |
163
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
3160-8
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pubmed:dateRevised |
2009-11-19
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pubmed:meshHeading |
pubmed-meshheading:10477583-Animals,
pubmed-meshheading:10477583-Antibodies, Anti-Idiotypic,
pubmed-meshheading:10477583-B-Lymphocytes,
pubmed-meshheading:10477583-CDC2-CDC28 Kinases,
pubmed-meshheading:10477583-Cell Cycle Proteins,
pubmed-meshheading:10477583-Cell Differentiation,
pubmed-meshheading:10477583-Cyclin D,
pubmed-meshheading:10477583-Cyclin E,
pubmed-meshheading:10477583-Cyclin-Dependent Kinase 2,
pubmed-meshheading:10477583-Cyclin-Dependent Kinase 4,
pubmed-meshheading:10477583-Cyclin-Dependent Kinase 6,
pubmed-meshheading:10477583-Cyclin-Dependent Kinase 9,
pubmed-meshheading:10477583-Cyclin-Dependent Kinase Inhibitor p27,
pubmed-meshheading:10477583-Cyclin-Dependent Kinases,
pubmed-meshheading:10477583-Cyclins,
pubmed-meshheading:10477583-DNA,
pubmed-meshheading:10477583-Enzyme Activation,
pubmed-meshheading:10477583-G1 Phase,
pubmed-meshheading:10477583-Holoenzymes,
pubmed-meshheading:10477583-Immunoglobulin Fab Fragments,
pubmed-meshheading:10477583-Mice,
pubmed-meshheading:10477583-Mice, Inbred BALB C,
pubmed-meshheading:10477583-Microtubule-Associated Proteins,
pubmed-meshheading:10477583-Phosphorylation,
pubmed-meshheading:10477583-Protein-Serine-Threonine Kinases,
pubmed-meshheading:10477583-Proto-Oncogene Proteins,
pubmed-meshheading:10477583-RNA,
pubmed-meshheading:10477583-Receptors, Antigen, B-Cell,
pubmed-meshheading:10477583-Receptors, IgG,
pubmed-meshheading:10477583-Retinoblastoma Protein,
pubmed-meshheading:10477583-Tumor Suppressor Proteins,
pubmed-meshheading:10477583-Up-Regulation
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pubmed:year |
1999
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pubmed:articleTitle |
B cell antigen receptor-mediated activation of cyclin-dependent retinoblastoma protein kinases and inhibition by co-cross-linking with Fc gamma receptors.
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pubmed:affiliation |
Department of Biology, Boston College, Chestnut Hill, MA 02467, 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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