Differential regulation of p34(cdc2) and p33(cdk2) by transforming growth factor-β1 in murine mammary epithelial cells

Michael P Fautsch, S. T. Eblen, R. A. Anders, R. J. Burnette, Edward B Leof

Research output: Contribution to journalArticle

11 Citations (Scopus)

Abstract

Cyclin-dependent kinases (cdks) are a family of proteins whose function plays a critical role in cell cycle traverse. Transforming growth factor- β1 (TGF-β1) is a potent growth inhibitor of epithelial cells. Since cdks have been suggested as possible biochemical markers for TGF-β growth inhibition, we investigated the effect of TGF-β1 on cdc2 and cdk2 in a normal mouse mammary epithelial cell line (MME) and a TGF-β-resistant MME cell line (BG18.2). TGF-β1 decreases newly synthesized cdc2 protein levels within 6 h after addition. Coincident with this decrease in newly synthesized cdc2 protein was a marked reduction in its ability to phosphorylate histone H1. This decrease in kinase activity is not due to a change in steady-state levels of cdc2 protein, since mRNA and total protein levels of cdc2 are not reduced until 12 h after TGF-β1 addition. This suggests that the kinase activity of cdc2 is dependent on newly synthesized cdc2 protein. Moreover, the protein synthesis of another cyclin-dependent kinase, cdk2, is not effected by TGF-β1 addition, but its kinase activity is substantially reduced. Thus, it appears that TGF-β decreases the kinase activity of both cdc2 and cdk2 by distinct mechanisms.

Original languageEnglish (US)
Pages (from-to)517-526
Number of pages10
JournalJournal of Cellular Biochemistry
Volume58
Issue number4
DOIs
StatePublished - 1995

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CDC2 Protein Kinase
Transforming Growth Factors
Breast
Epithelial Cells
Cyclin-Dependent Kinases
Phosphotransferases
Cells
Cell Line
Growth Inhibitors
Proteins
Histones
Cell Cycle
Biomarkers
Messenger RNA
Growth

Keywords

  • cell cycle
  • cyclin-dependent kinase
  • serine-threonine kinase

ASJC Scopus subject areas

  • Biochemistry
  • Cell Biology

Cite this

Differential regulation of p34(cdc2) and p33(cdk2) by transforming growth factor-β1 in murine mammary epithelial cells. / Fautsch, Michael P; Eblen, S. T.; Anders, R. A.; Burnette, R. J.; Leof, Edward B.

In: Journal of Cellular Biochemistry, Vol. 58, No. 4, 1995, p. 517-526.

Research output: Contribution to journalArticle

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