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Phosphorylation at tyrosine 262 promotes GADD34 protein turnover.

Publication ,  Journal Article
Zhou, W; Jeyaraman, K; Yusoff, P; Shenolikar, S
Published in: J Biol Chem
November 15, 2013

In mammalian cells, metabolic and environmental stress increases the phosphorylation of the eukaryotic translational initiation factor, eIF2α, and attenuates global protein synthesis. Subsequent transcriptional activation of GADD34 assembles an eIF2α phosphatase that feeds back to restore mRNA translation. Active proteasomal degradation of GADD34 protein then reestablishes the sensitivity of cells to subsequent bouts of stress. Mass spectrometry established GADD34 phosphorylation on multiple serines, threonines, and tyrosines. Phosphorylation at tyrosine 262 enhanced the rate of the GADD34 protein turnover. Substrate-trapping studies identified TC-PTP (PTPN2) as a potential GADD34 phosphatase, recognizing phosphotyrosine 262. Reduced GADD34 protein levels in TC-PTP-null MEFs following ER stress emphasized the importance of TC-PTP in determining the cellular levels of GADD34 protein. The susceptibility of TC-PTP-null MEFs to ER stress-induced apoptosis was significantly ameliorated by ectopic expression of GADD34. The data suggested that GADD34 phosphorylation on tyrosine 262 modulates endoplasmic reticulum stress signaling and cell fate.

Duke Scholars

Published In

J Biol Chem

DOI

EISSN

1083-351X

Publication Date

November 15, 2013

Volume

288

Issue

46

Start / End Page

33146 / 33155

Location

United States

Related Subject Headings

  • Tyrosine
  • Signal Transduction
  • Proteolysis
  • Protein Tyrosine Phosphatase, Non-Receptor Type 2
  • Protein Phosphatase 1
  • Phosphorylation
  • Mice, Knockout
  • Mice
  • Humans
  • Hela Cells
 

Citation

APA
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ICMJE
MLA
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Zhou, W., Jeyaraman, K., Yusoff, P., & Shenolikar, S. (2013). Phosphorylation at tyrosine 262 promotes GADD34 protein turnover. J Biol Chem, 288(46), 33146–33155. https://doi.org/10.1074/jbc.M113.504407
Zhou, Wei, Krishna Jeyaraman, Permeen Yusoff, and Shirish Shenolikar. “Phosphorylation at tyrosine 262 promotes GADD34 protein turnover.J Biol Chem 288, no. 46 (November 15, 2013): 33146–55. https://doi.org/10.1074/jbc.M113.504407.
Zhou W, Jeyaraman K, Yusoff P, Shenolikar S. Phosphorylation at tyrosine 262 promotes GADD34 protein turnover. J Biol Chem. 2013 Nov 15;288(46):33146–55.
Zhou, Wei, et al. “Phosphorylation at tyrosine 262 promotes GADD34 protein turnover.J Biol Chem, vol. 288, no. 46, Nov. 2013, pp. 33146–55. Pubmed, doi:10.1074/jbc.M113.504407.
Zhou W, Jeyaraman K, Yusoff P, Shenolikar S. Phosphorylation at tyrosine 262 promotes GADD34 protein turnover. J Biol Chem. 2013 Nov 15;288(46):33146–33155.

Published In

J Biol Chem

DOI

EISSN

1083-351X

Publication Date

November 15, 2013

Volume

288

Issue

46

Start / End Page

33146 / 33155

Location

United States

Related Subject Headings

  • Tyrosine
  • Signal Transduction
  • Proteolysis
  • Protein Tyrosine Phosphatase, Non-Receptor Type 2
  • Protein Phosphatase 1
  • Phosphorylation
  • Mice, Knockout
  • Mice
  • Humans
  • Hela Cells