Ras-induced and extracellular signal-regulated kinase 1 and 2 phosphorylation-dependent isomerization of protein tyrosine phosphatase (PTP)-PEST by PIN1 promotes FAK dephosphorylation by PTP-PEST.

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.
Authors	Yanhua Zheng, Weiwei Yang, Yan Xia, David Hawke, David X Liu, Zhimin Lu
Journal	Molecular and cellular biology (Mol Cell Biol) Vol. 31 Issue 21 Pg. 4258-69 (Nov 2011) ISSN: 1098-5549 [Electronic] United States
PMID	21876001 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, Non-P.H.S.)
Chemical References	NIMA-Interacting Peptidylprolyl Isomerase Focal Adhesion Kinase 1 PTK2 protein, human PTPN12 protein, human Protein Tyrosine Phosphatase, Non-Receptor Type 12 ras Proteins PIN1 protein, human Peptidylprolyl Isomerase Pin1 protein, mouse
Topics	Animals Cell Line, Transformed Cell Movement Disease Progression Focal Adhesion Kinase 1 (deficiency, genetics, metabolism) Focal Adhesions Genes, ras Humans Lung Neoplasms (metabolism, pathology, secondary) MAP Kinase Signaling System Mice Mice, Nude Models, Biological NIMA-Interacting Peptidylprolyl Isomerase Neoplasm Invasiveness Neoplasms (etiology, genetics, metabolism) Peptidylprolyl Isomerase (metabolism) Phosphorylation Protein Binding Protein Tyrosine Phosphatase, Non-Receptor Type 12 (deficiency, genetics, metabolism) ras Proteins (metabolism)

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