title: Protein phosphatase-2A regulates protein tyrosine phosphatase activity in Lewis lung carcinoma tumor variants.
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.
authors.affiliation: Department of Cell Biology, Loyola University Chicago, Stritch School of Medicine, Maywood, Illinois, USA.
authors.forename: Jodi L
authors.initials: JL
authors.lastname: Jackson
authors.forename: M Rita I
authors.initials: MR
authors.lastname: Young
mesh_terms: D000818:Animals; D015153:Blotting, Western; D018827:Carcinoma, Lewis Lung / Q000201:enzymology* / Q000473:pathology*; D003598:Cytoskeletal Proteins / Q000378:metabolism; D015536:Down-Regulation; D004791:Enzyme Inhibitors / Q000494:pharmacology; D047908:Intracellular Signaling Peptides and Proteins; D051379:Mice; D019319:Okadaic Acid / Q000494:pharmacology; D051419:Paxillin; D010749:Phosphoprotein Phosphatases / Q000037:antagonists & inhibitors / Q000502:physiology*; D010750:Phosphoproteins / Q000378:metabolism; D010766:Phosphorylation; D010768:Phosphoserine / Q000378:metabolism; D010769:Phosphothreonine / Q000378:metabolism; D019000:Phosphotyrosine / Q000378:metabolism; D011233:Precipitin Tests; D054648:Protein Phosphatase 2; D054592:Protein Tyrosine Phosphatase, Non-Receptor Type 11; D017027:Protein Tyrosine Phosphatases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D054593:SH2 Domain-Containing Protein Tyrosine Phosphatases; D014407:Tumor Cells, Cultured / Q000378:metabolism / Q000473:pathology*; D018909:src Homology Domains
chemical_list: D003598:Cytoskeletal Proteins; D004791:Enzyme Inhibitors; D047908:Intracellular Signaling Peptides and Proteins; D051419:Paxillin; D010750:Phosphoproteins; C496062:Pxn protein, mouse; D010769:Phosphothreonine; D010768:Phosphoserine; D019319:Okadaic Acid; D019000:Phosphotyrosine; D010749:Phosphoprotein Phosphatases; D054648:Protein Phosphatase 2; D054592:Protein Tyrosine Phosphatase, Non-Receptor Type 11; D017027:Protein Tyrosine Phosphatases; C516725:Ptpn11 protein, mouse; D054593:SH2 Domain-Containing Protein Tyrosine Phosphatases