Involvement of the cyclin-dependent kinase inhibitor p27Kip1 in negative signaling through the antigen-receptor of B lymphocytes.
Several lines of evidence suggest that interaction with antigens generates a negative signal via the antigen receptor of B lymphocytes (cell surface immunoglobulin; sIg), resulting in apoptosis, growth arrest or functional inactivation, and that activation of B cells requires an additional co-stimulatory signal such as a T cell-derived signal through the B cell membrane molecule CD40. In the B cell line WEHI-231, sIg crosslinking induces apoptosis and cell cycle arrest at the late G1 phase, both of which are reversed by CD40 signaling. Crosslinking of sIg reduces the activity of cyclin dependent kinase (Cdk)2 required for cell cycle progression in the late G1 phase by induction of a Cdk inhibitor (CKI) p27Kip1, but the induction of p27Kip1 is abrogated by CD40 signaling. These results strongly suggest that p27Kip1 plays some role in negative signaling via sIg, resulting in growth arrest of antigen-stimulated B cells.
Han
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H
Department of Medical Chemistry, Faculty of Medicine, Kyoto University, Japan.
Nomura
T
T
Honjo
T
T
Tsubata
T
T
D000818:Animals; D017209:Apoptosis; D001402:B-Lymphocytes / Q000166:cytology / Q000276:immunology / Q000502:physiology*; D019013:CD40 Antigens / Q000502:physiology; D042846:CDC2-CDC28 Kinases; D002453:Cell Cycle / Q000502:physiology*; D018797:Cell Cycle Proteins; D002455:Cell Division; D002460:Cell Line; D051357:Cyclin-Dependent Kinase 2; D050760:Cyclin-Dependent Kinase Inhibitor p27; D018844:Cyclin-Dependent Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D004791:Enzyme Inhibitors / Q000378:metabolism; D016193:G1 Phase; D051379:Mice; D008869:Microtubule-Associated Proteins / Q000096:biosynthesis / Q000378:metabolism*; D017346:Protein Serine-Threonine Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D011947:Receptors, Antigen, B-Cell / Q000502:physiology*; D015398:Signal Transduction; D025521:Tumor Suppressor Proteins
D019013:CD40 Antigens; C493961:Cdkn1b protein, mouse; D018797:Cell Cycle Proteins; D004791:Enzyme Inhibitors; D008869:Microtubule-Associated Proteins; D011947:Receptors, Antigen, B-Cell; D025521:Tumor Suppressor Proteins; D050760:Cyclin-Dependent Kinase Inhibitor p27; D017346:Protein Serine-Threonine Kinases; D042846:CDC2-CDC28 Kinases; C495893:Cdk2 protein, mouse; D051357:Cyclin-Dependent Kinase 2; D018844:Cyclin-Dependent Kinases