Abstract
AbstractWe have investigated the role of tyrosine phosphorylation of the cyclin-dependent kinase (cdk) inhibitor p27Kip1 using the acute promyelocytic leukemia cell line NB4 together with granulocyte colony-stimulating factor (G-CSF). Short-term G-CSF stimulation resulted in a rapid tyrosine dephosphorylation of p27Kip1 accompanied by a change in its binding preferences to cdks. On G-CSF stimulation, p27Kip1 dissociated from cdk4 and associated with cdk2. Binding assays with recombinant p27Kip1 confirmed that tyrosine-phosphorylated p27Kip1 preferentially bound to cdk4, whereas unphosphorylated protein preferentially associated with cdk2. In addition, studies with p27Kip1 point mutations revealed a decisive role of Tyr88 and Tyr89 in binding to cdk4. Furthermore, phosphorylation of Tyr88 and Tyr89 was accompanied by strong nuclear translocation of p27Kip1. Taken together, this report provides the first evidence that tyrosine phosphorylation of p27Kip1 plays a crucial role in binding to cdks and its subcellular localization. Moreover, both effects are mediated by application of G-CSF.
Bibliography
Kardinal, C., Dangers, M., Kardinal, A., Koch, A., Brandt, D. T., Tamura, T., & Welte, K. (2006). Tyrosine phosphorylation modulates binding preference to cyclin-dependent kinases and subcellular localization of p27Kip1 in the acute promyelocytic leukemia cell line NB4. Blood, 107(3), 1133â1140.
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Dates
Type | When |
---|---|
Created | 19 years, 10 months ago (Sept. 29, 2005, 8:24 p.m.) |
Deposited | 2 years, 3 months ago (May 4, 2023, 4:51 p.m.) |
Indexed | 2 months, 1 week ago (June 13, 2025, 4:46 a.m.) |
Issued | 19 years, 6 months ago (Feb. 1, 2006) |
Published | 19 years, 6 months ago (Feb. 1, 2006) |
Published Print | 19 years, 6 months ago (Feb. 1, 2006) |
@article{Kardinal_2006, title={Tyrosine phosphorylation modulates binding preference to cyclin-dependent kinases and subcellular localization of p27Kip1 in the acute promyelocytic leukemia cell line NB4}, volume={107}, ISSN={1528-0020}, url={http://dx.doi.org/10.1182/blood-2005-05-1771}, DOI={10.1182/blood-2005-05-1771}, number={3}, journal={Blood}, publisher={American Society of Hematology}, author={Kardinal, Christian and Dangers, Marc and Kardinal, Angelika and Koch, Alexandra and Brandt, Dominique Tobias and Tamura, Teruko and Welte, Karl}, year={2006}, month=feb, pages={1133–1140} }