Cell cycle and hormonal control of nuclear-cytoplasmic localization of the serum- and glucocorticoid-inducible protein kinase, Sgk, in mammary tumor cells: A novel convergence point of anti-proliferative and proliferative cell signaling pathways

Patricia Buse, Susan Tran, Ed Luther, Phan T. Phu, Gregory W. Aponte, Gary L. Firestone

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Abstract

The serum- and glucocorticoid-inducible kinase (sgk) is a novel serine/threonine protein kinase that is transcriptionally regulated in rat mammary tumor cells by serum under proliferative conditions or by glucocorticoids that induce a G1 cell cycle arrest. Our results establish that the subcellular distribution of Sgk is under stringent cell cycle and hormonal control. Sgk is localized to the perinuclear or cytoplasmic compartment as a 50-kDa hypophosphorylated protein in cells arrested in G1 by treatment with the synthetic glucocorticoid dexamethasone. In serum- stimulated cells, Sgk was transiently hyperphosphorylated and resided in the nucleus. Laser scanning cytometry, which monitors Sgk localization and DNA content in individual mammary tumor cells of an asynchronously growing population, revealed that Sgk actively shuttles between the nucleus (in S and G2/M) and the cytoplasm (in G1) in synchrony with the cell cycle. In cells synchronously released from the G1/S boundary, Sgk localized to the nucleus during progression through S phase. The forced retention of exogenous Sgk in either the cytoplasmic compartment, using a wild type sgk gene, or the nucleus, using a nuclear localization signal-containing sgk gene (NLS-Sgk), suppressed the growth and DNA synthesis of serum-stimulated cells. Thus, our study implicates the nuclear-cytoplasmic shuttling of sgk as a requirement for cell cycle progression and represents a novel convergence point of anti- proliferative and proliferative signaling in mammary tumor cells.

Original languageEnglish (US)
Pages (from-to)7253-7263
Number of pages11
JournalJournal of Biological Chemistry
Volume274
Issue number11
DOIs
StatePublished - Mar 12 1999
Externally publishedYes

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Cell signaling
Cell Cycle Checkpoints
Protein Kinases
Glucocorticoids
Tumors
Cells
Breast Neoplasms
Serum
Phosphotransferases
Cell Cycle
Laser Scanning Cytometry
Genes
G1 Phase Cell Cycle Checkpoints
Nuclear Localization Signals
Protein-Serine-Threonine Kinases
DNA
S Phase
Dexamethasone
Rats
Cytoplasm

ASJC Scopus subject areas

  • Biochemistry

Cite this

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title = "Cell cycle and hormonal control of nuclear-cytoplasmic localization of the serum- and glucocorticoid-inducible protein kinase, Sgk, in mammary tumor cells: A novel convergence point of anti-proliferative and proliferative cell signaling pathways",
abstract = "The serum- and glucocorticoid-inducible kinase (sgk) is a novel serine/threonine protein kinase that is transcriptionally regulated in rat mammary tumor cells by serum under proliferative conditions or by glucocorticoids that induce a G1 cell cycle arrest. Our results establish that the subcellular distribution of Sgk is under stringent cell cycle and hormonal control. Sgk is localized to the perinuclear or cytoplasmic compartment as a 50-kDa hypophosphorylated protein in cells arrested in G1 by treatment with the synthetic glucocorticoid dexamethasone. In serum- stimulated cells, Sgk was transiently hyperphosphorylated and resided in the nucleus. Laser scanning cytometry, which monitors Sgk localization and DNA content in individual mammary tumor cells of an asynchronously growing population, revealed that Sgk actively shuttles between the nucleus (in S and G2/M) and the cytoplasm (in G1) in synchrony with the cell cycle. In cells synchronously released from the G1/S boundary, Sgk localized to the nucleus during progression through S phase. The forced retention of exogenous Sgk in either the cytoplasmic compartment, using a wild type sgk gene, or the nucleus, using a nuclear localization signal-containing sgk gene (NLS-Sgk), suppressed the growth and DNA synthesis of serum-stimulated cells. Thus, our study implicates the nuclear-cytoplasmic shuttling of sgk as a requirement for cell cycle progression and represents a novel convergence point of anti- proliferative and proliferative signaling in mammary tumor cells.",
author = "Patricia Buse and Susan Tran and Ed Luther and Phu, {Phan T.} and Aponte, {Gregory W.} and Firestone, {Gary L.}",
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AU - Tran, Susan

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AU - Firestone, Gary L.

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