HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Li, G. Articles by Gelfand, E. W. Search for Related Content PubMed PubMed Citation Articles by Li, G. Articles by Gelfand, E. W.

Identification of Multiple Cell Cycle Regulatory Functions of p57^Kip2 in Human T Lymphocytes¹

Division of Cell Biology, Department of Pediatrics, National Jewish Medical and Research Center, Denver, CO 80206

The specific functions of p57^Kip2 in lymphocytes have not yet been fully elucidated. In this study, it is shown that p57^Kip2, which is a member of the Cip/Kip family of cyclin-dependent kinase inhibitors, is present in the nuclei of normal resting (G₀) T cells from peripheral blood and in the nuclei of the T cell-derived Jurkat cell line. Activation through the TCR results in rapid transport of cytoplasmic cyclin-dependent kinase 6 (cdk6) to nuclei, where it associates with cyclin D and p57^Kip2 in active enzyme complexes. Using purified recombinant proteins, it was shown in vitro that addition of p57^Kip2 protein to a mixture of cyclin D2 and cdk6 enhanced the association of the latter two proteins and resulted in phosphorylation of p57^Kip2. To probe further the function of p57^Kip2, Jurkat cells stably transfected with a plasmid encoding p57^Kip2 under control of an inducible (tetracycline) promoter were made. Induction of p57^Kip2 resulted in increased association of cdk6 with cyclin D3, without receptor-mediated T cell stimulation. The overall amounts of cdk6 and cyclin D3, and also of cdk4 and cyclin E, remained unchanged. Most notably, increased p57^Kip2 levels resulted in marked inhibition of both cyclin E- and cyclin A-associated cdk2 kinase activities and a decrease in cyclin A amounts. Therefore, although facilitating activation of cdk6, the ultimate outcome of p57^Kip2 induction was a decrease in DNA synthesis and cell proliferation. The results indicate that p57^Kip2 is involved in the regulation of several aspects of the T cell cycle.

This article has been cited by other articles:

				L. A. Wolfraim and J. J. Letterio Cutting Edge: p27Kip1 Deficiency Reduces the Requirement for CD28-Mediated Costimulation in Naive CD8+ but Not CD4+ T Lymphocytes J. Immunol., March 1, 2005; 174(5): 2481 - 2484. [Abstract] [Full Text] [PDF]