Cell cycle-specific induction of Cdk2 expression in B lymphocytes following antigen receptor cross-linking.
The ligation of membrane Ig (mIg) on quiescent primary B lymphocytes by mitogenic concentrations of anti-IgM antibodies leads to cell cycle progression. The level of cyclin-dependent kinase 2 (Cdk2) expression was found to be restricted to specific phases of the cell cycle in primary cultures of murine B lymphocytes. Resting G0 phase, G1 phase, or B cells arrested near the G1/S boundary by hydroxyurea contained no detectable Cdk2 protein or associated histone H1 kinase activity. In contrast, B cell entry into S phase was accompanied by an induction in the expression of cellular Cdk2 as judged by immunoblotting of B cell lysates with anti-Cdk2 antibodies. Concomitant with S phase entry was the detection of anti-Cdk2-specific immunoprecipitable histone H1 kinase activity. Further analysis revealed that the amount of cyclin A protein also oscillated during cell cycle, appearing initially in G1 phase B cells. Cyclin A was found to be associated with Cdk2 in B cells during S phase progression. These results indicate that cross-linking of mIg on primary B lymphocytes results in the "downstream" catalytic activation of Cdk2. The timing of Cdk2 expression and its association with cyclin A suggests that Cdk2 may not be involved in the decision to enter S phase, but rather may provide a role in the maintenance of S phase progression or in preparing B cells to enter M phase.
Department of Biology, Boston College, Chestnut Hill, MA 02167.
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Tanguay
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Chiles
D000818:Animals; D000888:Antibodies, Anti-Idiotypic / Q000494:pharmacology; D001402:B-Lymphocytes / Q000187:drug effects / Q000201:enzymology*; D042846:CDC2-CDC28 Kinases; D002453:Cell Cycle / Q000502:physiology*; D002478:Cells, Cultured; D051357:Cyclin-Dependent Kinase 2; D018844:Cyclin-Dependent Kinases; D016213:Cyclins / Q000096:biosynthesis; D004790:Enzyme Induction; D008213:Lymphocyte Activation; D016200:Maturation-Promoting Factor / Q000096:biosynthesis; D051379:Mice; D008807:Mice, Inbred BALB C; D011494:Protein Kinases / Q000096:biosynthesis*; D017346:Protein Serine-Threonine Kinases; D011947:Receptors, Antigen, B-Cell / Q000378:metabolism*; D016196:S Phase / Q000502:physiology
D000888:Antibodies, Anti-Idiotypic; D016213:Cyclins; D011947:Receptors, Antigen, B-Cell; C044203:anti-IgM; D011494:Protein Kinases; D017346:Protein Serine-Threonine Kinases; D042846:CDC2-CDC28 Kinases; C495893:Cdk2 protein, mouse; D051357:Cyclin-Dependent Kinase 2; D018844:Cyclin-Dependent Kinases; D016200:Maturation-Promoting Factor