Cutting edge: differential signaling requirements for activation of assembled cyclin D3-cdk4 complexes in B-1 and B-2 lymphocyte subsets.
B-1 lymphocytes represent a distinct B cell subset with unusual mitogenic responses. PMA alone promotes proliferation in B-1 cells, but not in splenic B-2 cells. Although cyclin D2-cyclin-dependent kinase 4 (cdk4) complexes mediate early retinoblastoma gene product (pRb) phosphorylation in B-1 cells, the transient nature of their accumulation cannot account for the continued increase in pRb phosphorylation, which is maximal at 24 h. We show herein that PMA promotes the accumulation of functional cyclin D3-cdk4 complexes in B-1 cells following loss of cyclin D2. PMA also induces accumulation of cyclin D3-cdk4 complexes in B-2 cells; however, these complexes do not phosphorylate pRb. Thus, PMA is sufficient to induce synthesis and assembly of cyclin D3-cdk4 complexes in B-1 and B-2 cells; however, PMA triggers cyclin D3-cdk4 activation only in B-1 cells. These results reveal a novel regulatory step that controls activation of cyclin D3-cdk4 complexes whose function segregates differentially in B cell subsets.
Department of Biology, Boston College, Chestnut Hill, MA 02467, USA.
D A
DA
Tanguay
T P
TP
Colarusso
C
C
Doughty
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S
Pavlovic-Ewers
T L
TL
Rothstein
T C
TC
Chiles
D000818:Animals; D016175:B-Lymphocyte Subsets / Q000166:cytology / Q000201:enzymology* / Q000276:immunology / Q000378:metabolism; D002455:Cell Division / Q000187:drug effects / Q000276:immunology; D002478:Cells, Cultured; D056743:Cyclin D3; D051358:Cyclin-Dependent Kinase 4; D018844:Cyclin-Dependent Kinases / Q000378:metabolism*; D016213:Cyclins / Q000378:metabolism*; D004789:Enzyme Activation / Q000187:drug effects / Q000276:immunology; D008213:Lymphocyte Activation / Q000187:drug effects; D046911:Macromolecular Substances; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D010766:Phosphorylation / Q000187:drug effects; D011518:Proto-Oncogene Proteins; D016160:Retinoblastoma Protein / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects / Q000276:immunology*; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology
C534697:Ccnd3 protein, mouse; D056743:Cyclin D3; D016213:Cyclins; D046911:Macromolecular Substances; D011518:Proto-Oncogene Proteins; D016160:Retinoblastoma Protein; C495902:Cdk4 protein, mouse; D051358:Cyclin-Dependent Kinase 4; D018844:Cyclin-Dependent Kinases; D013755:Tetradecanoylphorbol Acetate