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Protein phosphatase-2A regulates protein tyrosine phosphatase activity in Lewis lung carcinoma tumor variants

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Abstract

Cellular adherence and motility are processes that are controlled by focal adhesion assembly and disassembly. Consequently, the dynamics of focal adhesions regulate tumor cell metastasis and are influenced by the tyrosine phosphorylation state of paxillin. Metastatic LLC cells are more migratory and have reduced paxillin tyrosine phosphorylation as compared to nonmetastatic LLC cells. In nonmetastatic Lewis lung carcinoma (LLC) tumor cells, inhibition of the serine/threonine protein phosphatase-2A (PP-2A) activity results in increased motility that is associated with a reduction in the phosphotyrosine content of paxillin. Studies to determine if PP-2A can regulate protein tyrosine phosphatase activity showed that blocking PP-2A activity of nonmetastatic LLC-C8 tumor cells with okadaic acid reduces protein tyrosine phosphatase activity. Among the tyrosine phosphatases whose activity was inhibited upon PP-2A inhibition is Shp-2. In contrast, protein levels of Shp-2 are unaffected by PP-2A inhibition. While these results do not fully identify how inhibition of PP-2A results in tyrosine dephosphorylation of paxillin, they do demonstrate that PP-2A can link serine/threonine and tyrosine signaling pathways by regulating protein tyrosine phosphatases.

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Authors and Affiliations

  1. Departments of Cell Biology, Neurobiology and Anatomy, USA

    Jodi L. Jackson

  2. Pathology, USA

    M. Rita I. Young

  3. Otolaryngology, Loyola University Chicago, Stritch School of Medicine, Maywood, Illinois, USA

    M. Rita I. Young

  4. Research Services, Hines VA Hospital, Hines, Illinois, USA

    M. Rita I. Young

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  1. Jodi L. Jackson
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Correspondence to M. Rita I. Young.

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Jackson, J.L., Young, M.R.I. Protein phosphatase-2A regulates protein tyrosine phosphatase activity in Lewis lung carcinoma tumor variants. Clin Exp Metastasis 20, 357–364 (2003). https://doi.org/10.1023/A:1024012000009

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