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

Authors
  • Liang, Fubo
  • Luo, Yong
  • Dong, Yuanshu
  • Walls, Chad D
  • Liang, Jiao
  • Jiang, Hao-Yuan
  • Sanford, Jeremy R
  • Wek, Ronald C
  • Zhang, Zhong-Yin
Type
Published Article
Journal
Journal of Biological Chemistry
Publisher
American Society for Biochemistry & Molecular Biology (ASBMB)
Publication Date
Apr 18, 2008
Volume
283
Issue
16
Pages
10339–10346
Identifiers
DOI: 10.1074/jbc.M708285200
PMID: 18268019
Source
Medline
License
Unknown

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.

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