ArticleBMC cell biology2008
Phosphorylation of p130Cas initiates Rac activation and membrane ruffling.
Article in BMC cell biology, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 45 papers.
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Who cites it
45 citing papers in PubMed, 67 citations in OpenAlex.
- FAK and p130Cas Modulate Stiffness-Mediated Early Transcription and Cellular Metabolism.Cytoskeleton (Hoboken, N.J.) · 2025Article
- Focal Adhesion Kinase and Colony Stimulating Factors: Intestinal Homeostasis and Innate Immunity Crosstalk.Cells · 2024Review
- FAK and p130Cas modulate stiffness-mediated early transcription and cellular metabolism.bioRxiv : the preprint server for biology · 2024Article
- Systems Pharmacodynamic Model of Combined Gemcitabine and Trabectedin in Pancreatic Cancer Cells. Part I: Effects on Signal Transduction Pathways Related to Tumor GrowthJournal of pharmaceutical sciences · 2024Article
- An adhesion signaling axis involving Dystroglycan, β1-Integrin, and Cas adaptor proteins regulates the establishment of the cortical glial scaffold.PLoS biology · 2023Article
- BTG1 inactivation drives lymphomagenesis and promotes lymphoma dissemination through activation of BCAR1.Blood · 2023Article
- Gut homeostasis, injury, and healing: New therapeutic targets.World journal of gastroenterology · 2022Review
- Manipulating oligodendrocyte intrinsic regeneration mechanism to promote remyelination.Cellular and molecular life sciences : CMLS · 2021Review
- Article
- The Arp2/3 complex is crucial for colonisation of the mouse skin by melanoblasts.Development (Cambridge, England) · 2020Article
- CSRP2 suppresses colorectal cancer progressionTheranostics · 2020Article
- The Role of CTHRC1 in Regulation of Multiple Signaling and Tumor Progression and Metastasis.Mediators of inflammation · 2020Review
- The Mechanisms Underlying PTEN Loss in Human Tumors Suggest Potential Therapeutic Opportunities.Biomolecules · 2019Review
- CRKL Mediates p110β-Dependent PI3K Signaling in PTEN-Deficient Cancer Cells.Cell reports · 2017Article
- ARHGAP42 is activated by Src-mediated tyrosine phosphorylation to promote cell motility.Journal of cell science · 2017Article
- Redox control of Cas phosphorylation requires Abl kinase in regulation of intestinal epithelial cell spreading and migration.American journal of physiology. Gastrointestinal and liver physiology · 2016Article
- A ligand-independent integrin β1 mechanosensory complex guides spindle orientation.Nature communications · 2016Article
- Functions of the Tumor Suppressors p53 and Rb in Actin Cytoskeleton Remodeling.BioMed research international · 2016Review
- The molecular effect of metastasis suppressors on Src signaling and tumorigenesis: new therapeutic targets.Oncotarget · 2015Review
- FUSE Binding Protein 1 Facilitates Persistent Hepatitis C Virus Replication in Hepatoma Cells by Regulating Tumor Suppressor p53.Journal of virology · 2015Article
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Authors and funding
2 authors at 1 institution in 1 country.
Funding
Abstract
backgroundNon-receptor tyrosine kinases (NTKs) regulate physiological processes such as cell migration, differentiation, proliferation, and survival by interacting with and phosphorylating a large number of substrates simultaneously. This makes it difficult to attribute a particular biological effect to the phosphorylation of a particular substrate. We developed the Functional Interaction Trap (FIT) method to phosphorylate specifically a single substrate of choice in living cells, thereby allowing the biological effect(s) of that phosphorylation to be assessed. In this study we have used FIT to investigate the effects of specific phosphorylation of p130Cas, a protein implicated in cell migration. We have also used this approach to address a controversy regarding whether it is Src family kinases or focal adhesion kinase (FAK) that phosphorylates p130Cas in the trimolecular Src-FAK-p130Cas complex.
resultsWe show here that SYF cells (mouse fibroblasts lacking the NTKs Src, Yes and Fyn) exhibit a low level of basal tyrosine phosphorylation at focal adhesions. FIT-mediated tyrosine phosphorylation of NTK substrates p130Cas, paxillin and FAK and cortactin was observed at focal adhesions, while FIT-mediated phosphorylation of cortactin was also seen at the cell periphery. Phosphorylation of p130Cas in SYF cells led to activation of Rac1 and increased membrane ruffling and lamellipodium formation, events associated with cell migration. We also found that the kinase activity of Src and not FAK is essential for phosphorylation of p130Cas when the three proteins exist as a complex in focal adhesions.
conclusionThese results demonstrate that tyrosine phosphorylation of p130Cas is sufficient for its localization to focal adhesions and for activation of downstream signaling events associated with cell migration. FIT provides a valuable tool to evaluate the contribution of individual components of the response to signals with multiple outputs, such as activation of NTKs.
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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.