Abstract
Protein tyrosine phosphatase (PTP)-PEST is a critical regulator of cell adhesion and migration. However, the mechanism by which PTP-PEST is regulated in response to oncogenic signaling to dephosphorylate its substrates remains unclear. Here, we demonstrate that activated Ras induces extracellular signal-regulated kinase 1 and 2-dependent phosphorylation of PTP-PEST at S571, which recruits PIN1 to bind to PTP-PEST. Isomerization of the phosphorylated PTP-PEST by PIN1 increases the interaction between PTP-PEST and FAK, which leads to the dephosphorylation of FAK Y397 and the promotion of migration, invasion, and metastasis of v-H-Ras-transformed cells. These findings uncover an important mechanism for the regulation of PTP-PEST in activated Ras-induced tumor progression.
Publication types
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Research Support, N.I.H., Extramural
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, Non-P.H.S.
MeSH terms
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Animals
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Cell Line, Transformed
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Cell Movement
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Disease Progression
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Focal Adhesion Kinase 1 / deficiency
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Focal Adhesion Kinase 1 / genetics
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Focal Adhesion Kinase 1 / metabolism*
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Focal Adhesions
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Genes, ras
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Humans
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Lung Neoplasms / metabolism
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Lung Neoplasms / pathology
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Lung Neoplasms / secondary
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MAP Kinase Signaling System*
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Mice
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Mice, Nude
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Models, Biological
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NIMA-Interacting Peptidylprolyl Isomerase
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Neoplasm Invasiveness
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Neoplasms / etiology
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Neoplasms / genetics
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Neoplasms / metabolism
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Peptidylprolyl Isomerase / metabolism*
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Phosphorylation
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Protein Binding
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Protein Tyrosine Phosphatase, Non-Receptor Type 12 / deficiency
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Protein Tyrosine Phosphatase, Non-Receptor Type 12 / genetics
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Protein Tyrosine Phosphatase, Non-Receptor Type 12 / metabolism*
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ras Proteins / metabolism*
Substances
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NIMA-Interacting Peptidylprolyl Isomerase
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Focal Adhesion Kinase 1
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PTK2 protein, human
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PTPN12 protein, human
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Protein Tyrosine Phosphatase, Non-Receptor Type 12
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ras Proteins
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PIN1 protein, human
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Peptidylprolyl Isomerase
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Pin1 protein, mouse