Translational Control of C-terminal Src Kinase (Csk) Expression by PRL3 Phosphatase*
| Autor: | Zhong Yin Zhang, Jeremy R. Sanford, Hao Yuan Jiang, Yong Luo, Ronald C. Wek, Jiao Liang, Fubo Liang, Yuanshu Dong, Chad D. Walls |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2008 |
| Předmět: |
Cell signaling
Phosphatase Eukaryotic Initiation Factor-2 Protein tyrosine phosphatase Biology Biochemistry Models Biological Gene Expression Regulation Enzymologic Cell Line CSK Tyrosine-Protein Kinase Humans RNA Messenger Neoplasm Metastasis Phosphorylation Molecular Biology Regulation of gene expression eIF2 Tyrosine-protein kinase CSK Protein Synthesis Post-Translational Modification and Degradation Cell Biology Protein-Tyrosine Kinases Neoplasm Proteins src-Family Kinases Gene Expression Regulation Polyribosomes Protein Biosynthesis Cancer research Protein Tyrosine Phosphatases Proto-oncogene tyrosine-protein kinase Src Peptide Hydrolases |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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