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Blood, 1 February 2006, Vol. 107, No. 3, pp. 1133-1140. Prepublished online as a Blood First Edition Paper on September 29, 2005; DOI 10.1182/blood-2005-05-1771. This Article Full Text (PDF) Supplemental Figure All Versions of this Article: 2005-05-1771v1 107/3/1133    most recent Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Kardinal, C. Articles by Welte, K. Search for Related Content PubMed PubMed Citation Articles by Kardinal, C. Articles by Welte, K. Social Bookmarking                   What's this?  Previous Article  |  Next Article  Submitted May 2, 2005 Accepted September 20, 2005 Tyrosine phosphorylation modulates binding preference to cyclin-dependent kinases and subcellular localization of p27Kip1 in the acute promyelocytic leukemia cell line NB4 Christian Kardinal*, Marc Dangers, Angelika Kardinal, Alexandra Koch, Dominique T Brandt, Teruko Tamura, and Karl Welte Padiatrische Hamatologie und Onkologie, Medizinische Hochschule Hannover (MHH), Hannover, Germany Nephrologie, Medizinische Hochschule Hannover, Hannover, Germany Lehrstuhl fur Angewandte Physik, Universitat Munchen, Munchen, Germany Institut fur Biochemie, Medizinische Hochschule Hannover, Hannover, Germany Pharmakologisches Institut, Universitat Heidelberg, Heidelberg, Germany * Corresponding author; email: Kardinal.Christian{at}mh-hannover.de. We 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. Upon 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. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: E. Susaki, K. Nakayama, L. Yamasaki, and K. I. Nakayama Common and specific roles of the related CDK inhibitors p27 and p57 revealed by a knock-in mouse model PNAS, March 31, 2009; 106(13): 5192 - 5197. [Abstract] [Full Text] [PDF] M. D. Larrea, J. Liang, T. Da Silva, F. Hong, S. H. Shao, K. Han, D. Dumont, and J. M. Slingerland Phosphorylation of p27Kip1 Regulates Assembly and Activation of Cyclin D1-Cdk4 Mol. Cell. Biol., October 15, 2008; 28(20): 6462 - 6472. [Abstract] [Full Text] [PDF] Z. Guo, L. Qian, R. Liu, H. Dai, M. Zhou, L. Zheng, and B. Shen Nucleolar Localization and Dynamic Roles of Flap Endonuclease 1 in Ribosomal DNA Replication and Damage Repair Mol. Cell. Biol., July 1, 2008; 28(13): 4310 - 4319. [Abstract] [Full Text] [PDF] M. K. James, A. Ray, D. Leznova, and S. W. Blain Differential Modification of p27Kip1 Controls Its Cyclin D-cdk4 Inhibitory Activity Mol. Cell. Biol., January 1, 2008; 28(1): 498 - 510. [Abstract] [Full Text] [PDF]

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