E2F1, B-myb and selective members of cyclin/cdk subunits are targets for protein kinase C-mediated bimodal growth regulation in vascular endothelial cells.
In human umbilical vein endothelial cells, the protein kinase C (PKC) stimulation during the early G1 phase leads to potentiations in growth factor-stimulated DNA synthesis, the activation of cdc2 and cdk2 cyclin-dependent kinases, and the mRNA expression of cdc2, cyclins A, D1 and E, but not cdk2 or cdk4. Conversely, the PKC stimulation in the late G1 phase completely inhibits DNA synthesis, the activation of cyclin-dependent kinases, and the mRNA expression of the same set of molecules except cyclin D1. Further, we found that the PKC stimulation bimodally regulates the message levels of E2F1 and B-myb, which are transcription factors implicated in the control of the mammalian cell cycle progression. These results indicate that the PKC signal transduction pathway, depending on the timing of activation in the G1 phase, either positively or negatively regulates the message level of growth-regulating genes that are crucial for the G1 to S phase progression.
Zhou
W
W
Department of Cardiovascular Biology, Faculty of Medicine, University of Tokyo, Japan.
Takuwa
N
N
Kumada
M
M
Takuwa
Y
Y
D042846:CDC2-CDC28 Kinases; D002352:Carrier Proteins; D002453:Cell Cycle; D018797:Cell Cycle Proteins; D051357:Cyclin-Dependent Kinase 2; D051358:Cyclin-Dependent Kinase 4; D018844:Cyclin-Dependent Kinases; D016213:Cyclins / Q000502:physiology*; D004268:DNA-Binding Proteins / Q000378:metabolism*; D050684:E2F Transcription Factors; D050687:E2F1 Transcription Factor; D004730:Endothelium, Vascular / Q000166:cytology*; D015870:Gene Expression; D006801:Humans; D011493:Protein Kinase C / Q000502:physiology*; D011494:Protein Kinases / Q000378:metabolism*; D017346:Protein Serine-Threonine Kinases; D011518:Proto-Oncogene Proteins; D012333:RNA, Messenger / Q000235:genetics; D056465:Retinoblastoma-Binding Protein 1; D015534:Trans-Activators; D050680:Transcription Factor DP1; D014157:Transcription Factors / Q000378:metabolism*
D002352:Carrier Proteins; D018797:Cell Cycle Proteins; D016213:Cyclins; D004268:DNA-Binding Proteins; D050684:E2F Transcription Factors; D050687:E2F1 Transcription Factor; C493753:E2F1 protein, human; C064352:MYBL2 protein, human; D011518:Proto-Oncogene Proteins; D012333:RNA, Messenger; D056465:Retinoblastoma-Binding Protein 1; D015534:Trans-Activators; D050680:Transcription Factor DP1; D014157:Transcription Factors; D011494:Protein Kinases; D017346:Protein Serine-Threonine Kinases; D011493:Protein Kinase C; D042846:CDC2-CDC28 Kinases; C495894:CDK2 protein, human; C495900:CDK4 protein, human; D051357:Cyclin-Dependent Kinase 2; D051358:Cyclin-Dependent Kinase 4; D018844:Cyclin-Dependent Kinases