1999
DOI: 10.1038/sj.onc.1202347
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Cell cycle start from quiescence controlled by tyrosine phosphorylation of Cdk4

Abstract: In mammals Cdk4 (or Cdk6 in some cell types) is required for starting the cell cycle. Recently we showed that Cdk4 is regulated by tyrosine phosphorylation and dephosphorylation, and that this regulation is required for a DNA damage-induced G 1 arrest. We report here that a generic anti-phosphotyrosine antibody can detect tyrosine-phosphorylated Cdk4 and that as revealed by immunoblot detection and kinase assay, this regulation is employed for DNA damage-responsive checkpoint control during cell cycle start fr… Show more

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Cited by 45 publications
(54 citation statements)
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“…CAK is generally considered to be constitutively active during cell cycle [37], but this should be demonstrated in our system. Very recently, the inhibitory tyrosine phosphorylation of CDK4 has been reported to be involved not only in DNA damage-induced G1 arrest, but also in regular cell's arrest in quiescence [38]. However, using the PY20 antibody we failed to detect the presence of phosphotyrosine in CDK4 immunoprecipitates of quiescent dog thyrocytes (negative data not shown).…”
Section: Discussionmentioning
confidence: 74%
“…CAK is generally considered to be constitutively active during cell cycle [37], but this should be demonstrated in our system. Very recently, the inhibitory tyrosine phosphorylation of CDK4 has been reported to be involved not only in DNA damage-induced G1 arrest, but also in regular cell's arrest in quiescence [38]. However, using the PY20 antibody we failed to detect the presence of phosphotyrosine in CDK4 immunoprecipitates of quiescent dog thyrocytes (negative data not shown).…”
Section: Discussionmentioning
confidence: 74%
“…This is in contrast to stimulation of Kit-225 cells by IL-2, which increased the steady-state levels of CDK4 mRNA by ϳ4-fold. Small increases in CDK4 protein were observed in Kit-225 cells stimulated by IL-2 for 1-3 h, but CDK4 activity increased by ϳ2-to 8-fold, suggesting IL-2 mediates additional events required for assembly and activation of active holoenzyme complexes (31,33). CDK4 activity was essentially abrogated in Kit-225 cells treated with anti-CD3, PHA, or PMA, and it could only be partially rescued by IL-2.…”
Section: Discussionmentioning
confidence: 95%
“…A critical role for CDK4 in cell cycle entry and the early stages of progression through the G 1 phase have been demonstrated in various cultured cell lines (31,32). However, it is generally believed that a growth factor signal is required to promote assembly and activation of active CDK4 complexes (33)(34)(35)(36).…”
Section: Discussionmentioning
confidence: 99%
“…In mammals, execution of D cyclin-dependent kinases is essential for onset of S phase (Baldin et al, 1993;Bates et al, 1994;Hengstschlager et al, 1999;Jinno et al, 1999a). Fibroblasts express D1 and D3 as major D cyclins and Cdk4 and Cdk6 as their kinase partners (Bates et al, 1994;Sherr, 1995).…”
Section: Introductionmentioning
confidence: 99%