Title

Cell cycling through Cdc25A - Transducer of cytokine proliferative signals

Authors

Authors

C. Kittipatarin; W. Q. Li; D. V. Bulavin; S. K. Durum;A. R. Khaled

Comments

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Abbreviated Journal Title

Cell Cycle

Keywords

interleukin-7; lymphocyte; p38 MAPK; homeostasis; Cdc25A; cell cycle; p27kip1; growth arrest; proliferation; cytokine; RECEPTOR-DEFICIENT MICE; DEFECTIVE LYMPHOID DEVELOPMENT; DEPENDENT; KINASE INHIBITOR; RESCUES T-LYMPHOPOIESIS; COMMON GAMMA-CHAIN; S-PHASE; CHECKPOINT; IN-VIVO; HOMEOSTATIC PROLIFERATION; INTRACELLULAR PH; CDK; INHIBITORS; Cell Biology

Abstract

A balance between survival and proliferative signals maintains a constant number of T lymphocytes that populate the mammalian immune system, a process termed "homeostasis". Central to this process is the availability of a stromal cell product-the cytokine interleukin-7 (IL-7). We recently showed that IL-7, in addition to protecting cells from apoptosis, drives the cell cycling of lymphocytes through regulation of the stability of the phosphatase, Cdc25A, a key activator of cyclin-dependent kinases (cdks). IL-7 achieves this by controlling the activity of p38 MAP kinase (MAPK), which can phosphorylate Cdc25A, triggering its degradation. Sustained expression of Cdc25A had diverse effects: it promoted cell cycling, even in presence of cell cycle inhibitors such p27(Kip1), and prevented cell shrinkage in response to cytokine deprivation. Herein we show a role for Cdc25A as a transducer of cytokine-driven proliferation and discuss novel implications for cell growth from the perspective of the requirements for maintenance of lymphocyte homeostasis.

Journal Title

Cell Cycle

Volume

5

Issue/Number

9

Publication Date

1-1-2006

Document Type

Article

Language

English

First Page

907

Last Page

912

WOS Identifier

WOS:000238575200001

ISSN

1538-4101

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