title: 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.affiliation: Brain Tumor Center and Department of Neuro-Oncology, The University of Texas M. D. Anderson Cancer Center, Houston, TX 77030, USA.
authors.forename: Yanhua
authors.initials: Y
authors.lastname: Zheng
authors.forename: Weiwei
authors.initials: W
authors.lastname: Yang
authors.forename: Yan
authors.initials: Y
authors.lastname: Xia
authors.forename: David
authors.initials: D
authors.lastname: Hawke
authors.forename: David X
authors.initials: DX
authors.lastname: Liu
authors.forename: Zhimin
authors.initials: Z
authors.lastname: Lu
mesh_terms: D000818:Animals; D002461:Cell Line, Transformed; D002465:Cell Movement; D018450:Disease Progression; D051417:Focal Adhesion Kinase 1 / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D022001:Focal Adhesions; D011905:Genes, ras; D006801:Humans; D008175:Lung Neoplasms / Q000378:metabolism / Q000473:pathology / Q000556:secondary; D020935:MAP Kinase Signaling System; D051379:Mice; D008819:Mice, Nude; D008954:Models, Biological; D000072340:NIMA-Interacting Peptidylprolyl Isomerase; D009361:Neoplasm Invasiveness; D009369:Neoplasms / Q000209:etiology / Q000235:genetics / Q000378:metabolism; D019696:Peptidylprolyl Isomerase / Q000378:metabolism*; D010766:Phosphorylation; D011485:Protein Binding; D054594:Protein Tyrosine Phosphatase, Non-Receptor Type 12 / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D018631:ras Proteins / Q000378:metabolism*
chemical_list: D000072340:NIMA-Interacting Peptidylprolyl Isomerase; D051417:Focal Adhesion Kinase 1; C496050:PTK2 protein, human; C516738:PTPN12 protein, human; D054594:Protein Tyrosine Phosphatase, Non-Receptor Type 12; D018631:ras Proteins; C000606846:PIN1 protein, human; D019696:Peptidylprolyl Isomerase; C000606850:Pin1 protein, mouse