Translational control of C-terminal Src kinase (Csk) expression by PRL3 phosphatase

Fubo Liang, Yong Luo, Yuanshu Dong, Chad D. Walls, Jiao Liang, Hao Yuan Jiang, Jeremy R. Sanford, Ronald Wek, Zhong-Yin Zhang

Research output: Contribution to journalArticle

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Abstract

Phosphatase of regenerating liver 3 (PRL3) is up-regulated in cancer metastases. However, little is known of PRL3-mediated cellular signaling pathways. We previously reported that elevated PRL3 expression increases Src kinase activity, which likely contributes to the increased tumorigenesis and metastasis potential of PRL3. PRL3-induced Src activation is proposed to be indirect through down-regulation of Csk, a negative regulator of Src. Given the importance of PRL3 in tumor metastasis and the role of Csk in controlling Src activity, we addressed the mechanism by which PRL3 mediates Csk down-regulation. PRL3 is shown to exert a negative effect on Csk protein synthesis, rather than regulation of Csk mRNA levels or protein turnover. Interestingly, the preferential decrease in Csk protein synthesis is a consequence of increased eIF2 phosphorylation resulting from PRL3 expression. Reduced Csk synthesis also occurs in response to cellular stress that induces eIF2 phosphorylation, indicating that this regulatory mechanism may occur in response to a wider spectrum of cellular conditions known to direct translational control. Thus, we have uncovered a previously uncharacterized role for PRL3 in the gene-specific translational control of Csk expression.

Original languageEnglish
Pages (from-to)10339-10346
Number of pages8
JournalJournal of Biological Chemistry
Volume283
Issue number16
DOIs
StatePublished - Apr 18 2008

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Phosphoric Monoester Hydrolases
Liver
Phosphorylation
Neoplasm Metastasis
Down-Regulation
CSK tyrosine-protein kinase
Cell signaling
Proteins
src-Family Kinases
Tumors
Neoplasms
Carcinogenesis
Genes
Chemical activation
Messenger RNA

ASJC Scopus subject areas

  • Biochemistry
  • Cell Biology
  • Molecular Biology

Cite this

Translational control of C-terminal Src kinase (Csk) expression by PRL3 phosphatase. / Liang, Fubo; Luo, Yong; Dong, Yuanshu; Walls, Chad D.; Liang, Jiao; Jiang, Hao Yuan; Sanford, Jeremy R.; Wek, Ronald; Zhang, Zhong-Yin.

In: Journal of Biological Chemistry, Vol. 283, No. 16, 18.04.2008, p. 10339-10346.

Research output: Contribution to journalArticle

Liang, F, Luo, Y, Dong, Y, Walls, CD, Liang, J, Jiang, HY, Sanford, JR, Wek, R & Zhang, Z-Y 2008, 'Translational control of C-terminal Src kinase (Csk) expression by PRL3 phosphatase', Journal of Biological Chemistry, vol. 283, no. 16, pp. 10339-10346. https://doi.org/10.1074/jbc.M708285200
Liang, Fubo ; Luo, Yong ; Dong, Yuanshu ; Walls, Chad D. ; Liang, Jiao ; Jiang, Hao Yuan ; Sanford, Jeremy R. ; Wek, Ronald ; Zhang, Zhong-Yin. / Translational control of C-terminal Src kinase (Csk) expression by PRL3 phosphatase. In: Journal of Biological Chemistry. 2008 ; Vol. 283, No. 16. pp. 10339-10346.
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AB - Phosphatase of regenerating liver 3 (PRL3) is up-regulated in cancer metastases. However, little is known of PRL3-mediated cellular signaling pathways. We previously reported that elevated PRL3 expression increases Src kinase activity, which likely contributes to the increased tumorigenesis and metastasis potential of PRL3. PRL3-induced Src activation is proposed to be indirect through down-regulation of Csk, a negative regulator of Src. Given the importance of PRL3 in tumor metastasis and the role of Csk in controlling Src activity, we addressed the mechanism by which PRL3 mediates Csk down-regulation. PRL3 is shown to exert a negative effect on Csk protein synthesis, rather than regulation of Csk mRNA levels or protein turnover. Interestingly, the preferential decrease in Csk protein synthesis is a consequence of increased eIF2 phosphorylation resulting from PRL3 expression. Reduced Csk synthesis also occurs in response to cellular stress that induces eIF2 phosphorylation, indicating that this regulatory mechanism may occur in response to a wider spectrum of cellular conditions known to direct translational control. Thus, we have uncovered a previously uncharacterized role for PRL3 in the gene-specific translational control of Csk expression.

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