ArticleMolecular cell2009
FAK phosphorylation by ERK primes ras-induced tyrosine dephosphorylation of FAK mediated by PIN1 and PTP-PEST.
Article in Molecular cell, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 97 papers.
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97 citing papers in PubMed, 169 citations in OpenAlex.
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- Pin1 targets phosphorylated NCOA4 for K29/K48-linked ubiquitination to suppress ferritinophagy and ferroptosis in anaplastic thyroid cancer.Cell death & disease · 2026Article
- Activation of the FAK-MAPK/ERK1 pathway promotes intestinal epithelial cell sheet migration during fistula tract repair.Scientific reports · 2026Article
- Phosphoproteomic profiling reveals reversal of dysregulated kinase signaling by nitric oxide inhibition in the Shank3 mouse model of autism.Scientific reports · 2026Article
- Multi-omic analysis of the liver-breast axis reveals key hepatic mediators of breast cancer progression.Science China. Life sciences · 2026Review
- An Overview of the Mechanisms of HPV-Induced Cervical Cancer: The Role of Kinase Targets in Pathogenesis and Drug Resistance.Cancers · 2026Review
- DAZAP1 promotes cancer progression and chemotherapy resistance by stabilizing PIN1 protein in gastric cancer.Cell biology and toxicology · 2025Article
- RhoE downregulation leads to enhanced cholesterol biosynthesis and sorafenib resistance in hepatocellular carcinoma.The Journal of biological chemistry · 2025Article
- Dynamic rigidity changes enable rapid cell migration on soft substrates.Nature communications · 2025Article
- NSun2-Mediated tsRNAs Alleviate Liver Fibrosis via FAK Dephosphorylation.Cell proliferation · 2025Article
- Drug Combinations Targeting FAK and MEK Overcomes Tumor Heterogeneity in Glioblastoma.Pharmaceutics · 2025Article
- Combined inhibition of focal adhesion kinase and RAF/MEK elicits synergistic inhibition of melanoma growth and reduces metastases.Cell reports. Medicine · 2025Article
- A Rapid One-Pot Workflow for Sensitive Microscale Phosphoproteomics.Journal of proteome research · 2024Article
- Pin1-catalyzed conformational regulation after phosphorylation: A distinct checkpoint in cell signaling and drug discovery.Science signaling · 2024Review
- Farnesyl-transferase inhibitors show synergistic anticancer effects in combination with novel KRAS-G12C inhibitors.British journal of cancer · 2024Article
- Roles and inhibitors of FAK in cancer: current advances and future directions.Frontiers in pharmacology · 2024Review
- Polarized focal adhesion kinase activity within a focal adhesion during cell migration.Nature chemical biology · 2023Article
- Article
- The role of RAS oncogenes in controlling epithelial mechanics.Trends in cell biology · 2023Review
- Regulation of eukaryotic protein kinases by Pin1, a peptidyl-prolyl isomerase.Advances in biological regulation · 2023Article
37 more citing papers are in PubMed but not listed here.
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Authors and funding
12 authors at 6 institutions in 3 countries.
Funding
Abstract
Activated Ras has been found in many types of cancer. However, the mechanism underlying Ras-promoted tumor metastasis remains unclear. We demonstrate here that activated Ras induces tyrosine dephosphorylation and inhibition of FAK mediated by the Ras downstream Fgd1-Cdc42-PAK1-MEK-ERK signaling cascade. ERK phosphorylates FAK S910 and recruits PIN1 and PTP-PEST, which colocalize with FAK at the lamellipodia of migrating cells. PIN1 binding and prolyl isomerization of FAK cause PTP-PEST to interact with and dephosphorylate FAK Y397. Inhibition of FAK mediated by this signal relay promotes Ras-induced cell migration, invasion, and metastasis. These findings uncover the importance of sequential modification of FAK-by serine phosphorylation, isomerization, and tyrosine dephosphorylation--in the regulation of FAK activity and, thereby, in Ras-related tumor metastasis.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.