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Involvement of the MKK6-p38gamma cascade in gamma-radiation-induced cell cycle arrest.

Publication ,  Journal Article
Wang, X; McGowan, CH; Zhao, M; He, L; Downey, JS; Fearns, C; Wang, Y; Huang, S; Han, J
Published in: Mol Cell Biol
July 2000

The p38 group of kinases belongs to the mitogen-activated protein (MAP) kinase superfamily with structural and functional characteristics distinguishable from those of the ERK, JNK (SAPK), and BMK (ERK5) kinases. Although there is a high degree of similarity among members of the p38 group in terms of structure and activation, each member appears to have a unique function. Here we show that activation of p38gamma (also known as ERK6 or SAPK3), but not the other p38 isoforms, is required for gamma-irradiation-induced G(2) arrest. Activation of the MKK6-p38gamma cascade is sufficient to induce G(2) arrest in cells, and expression of dominant negative alleles of MKK6 or p38gamma allows cells to escape the DNA damage-induce G(2) delay. Activation of p38gamma is dependent on ATM and leads to activation of Cds1 (also known as Chk2). These data suggest a model in which activation of ATM by gamma irradiation leads to the activation of MKK6, p38gamma, and Cds1 and that activation of both MKK6 and p38gamma is essential for the proper regulation of the G(2) checkpoint in mammalian cells.

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Published In

Mol Cell Biol

DOI

ISSN

0270-7306

Publication Date

July 2000

Volume

20

Issue

13

Start / End Page

4543 / 4552

Location

United States

Related Subject Headings

  • p38 Mitogen-Activated Protein Kinases
  • cdc25 Phosphatases
  • Tumor Suppressor Proteins
  • Signal Transduction
  • Pyridines
  • Protein Serine-Threonine Kinases
  • Protein Kinases
  • Phosphorylation
  • Mitogen-Activated Protein Kinases
  • Mitogen-Activated Protein Kinase Kinases
 

Citation

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Wang, X., McGowan, C. H., Zhao, M., He, L., Downey, J. S., Fearns, C., … Han, J. (2000). Involvement of the MKK6-p38gamma cascade in gamma-radiation-induced cell cycle arrest. Mol Cell Biol, 20(13), 4543–4552. https://doi.org/10.1128/MCB.20.13.4543-4552.2000
Wang, X., C. H. McGowan, M. Zhao, L. He, J. S. Downey, C. Fearns, Y. Wang, S. Huang, and J. Han. “Involvement of the MKK6-p38gamma cascade in gamma-radiation-induced cell cycle arrest.Mol Cell Biol 20, no. 13 (July 2000): 4543–52. https://doi.org/10.1128/MCB.20.13.4543-4552.2000.
Wang X, McGowan CH, Zhao M, He L, Downey JS, Fearns C, et al. Involvement of the MKK6-p38gamma cascade in gamma-radiation-induced cell cycle arrest. Mol Cell Biol. 2000 Jul;20(13):4543–52.
Wang, X., et al. “Involvement of the MKK6-p38gamma cascade in gamma-radiation-induced cell cycle arrest.Mol Cell Biol, vol. 20, no. 13, July 2000, pp. 4543–52. Pubmed, doi:10.1128/MCB.20.13.4543-4552.2000.
Wang X, McGowan CH, Zhao M, He L, Downey JS, Fearns C, Wang Y, Huang S, Han J. Involvement of the MKK6-p38gamma cascade in gamma-radiation-induced cell cycle arrest. Mol Cell Biol. 2000 Jul;20(13):4543–4552.

Published In

Mol Cell Biol

DOI

ISSN

0270-7306

Publication Date

July 2000

Volume

20

Issue

13

Start / End Page

4543 / 4552

Location

United States

Related Subject Headings

  • p38 Mitogen-Activated Protein Kinases
  • cdc25 Phosphatases
  • Tumor Suppressor Proteins
  • Signal Transduction
  • Pyridines
  • Protein Serine-Threonine Kinases
  • Protein Kinases
  • Phosphorylation
  • Mitogen-Activated Protein Kinases
  • Mitogen-Activated Protein Kinase Kinases