ArticleOncogene2000
RAFTK/Pyk2 tyrosine kinase mediates the association of p190 RhoGAP with RasGAP and is involved in breast cancer cell invasion.
Article in Oncogene, 2000. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 34 papers.
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Who cites it
34 citing papers in PubMed, 95 citations in OpenAlex.
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- Galectin-3 promotes secretion of proteases that decrease epithelium integrity in human colon cancer cells.Cell death & disease · 2023Article
- DUSP5P1 promotes gastric cancer metastasis and platinum drug resistance.Oncogenesis · 2022Article
- The Non-receptor Tyrosine Kinase Pyk2 in Brain Function and Neurological and Psychiatric Diseases.Frontiers in synaptic neuroscience · 2021Review
- MET-Pyk2 Axis Mediates Acquired Resistance to FGFR Inhibition in Cancer Cells.Frontiers in oncology · 2021Article
- p190A RhoGAP induces CDH1 expression and cooperates with E-cadherin to activate LATS kinases and suppress tumor cell growth.Oncogene · 2020Article
- Role of Pyk2 in Human Cancers.Medical science monitor : international medical journal of experimental and clinical research · 2018Review
- Significance of PYK2 level as a prognosis predictor in patients with colon adenocarcinoma after surgical resection.OncoTargets and therapy · 2018Article
- Structural Basis for the Interaction between Pyk2-FAT Domain and Leupaxin LD Repeats.Biochemistry · 2016Article
- PYK2 integrates growth factor and cytokine receptors signaling and potentiates breast cancer invasion via a positive feedback loop.Oncotarget · 2015Article
- Microparticles Mediate the Intercellular Regulation of microRNA-503 and Proline-Rich Tyrosine Kinase 2 to Alter the Migration and Invasion Capacity of Breast Cancer Cells.Frontiers in oncology · 2014Article
- Non-receptor-tyrosine kinases integrate fast glucocorticoid signaling in hippocampal neurons.The Journal of biological chemistry · 2013Article
- Article
- PYK-2 is tyrosine phosphorylated after activation of pituitary adenylate cyclase activating polypeptide receptors in lung cancer cells.Journal of molecular neuroscience : MN · 2012Article
- Identification of targets of c-Src tyrosine kinase by chemical complementation and phosphoproteomics.Molecular & cellular proteomics : MCP · 2012Article
- The role of proline rich tyrosine kinase 2 (Pyk2) on cisplatin resistance in hepatocellular carcinoma.PloS one · 2011Article
- Cleavage of galectin-3 by matrix metalloproteases induces angiogenesis in breast cancer.International journal of cancer · 2010Article
- Pyk2 activation triggers epidermal growth factor receptor signaling and cell motility after wounding sheets of epithelial cells.The Journal of biological chemistry · 2010Article
- TrkB is highly expressed in NSCLC and mediates BDNF-induced the activation of Pyk2 signaling and the invasion of A549 cells.BMC cancer · 2010Article
- Mesenchymal migration as a therapeutic target in glioblastoma.Journal of oncology · 2010Article
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Authors and funding
8 authors at 3 institutions in 2 countries.
Funding
Abstract
Focal adhesions and actin cytoskeleton are involved in cell growth, shape and movement and in tumor invasion. Mitogen-induced changes in actin cytoskeleton are accompanied by changes in the tyrosine phosphorylation of several focal adhesion proteins. In this study, we have investigated the role of RAFTK, a cytoplasmic tyrosine kinase related to focal adhesion kinase (FAK), in heregulin-mediated signal transduction in breast cancer cells. Stimulation of T47D cells with heregulin (HRG) induced the tyrosine phosphorylation of RAFTK and the formation of a multiprotein complex. Analyses of the members of the HRG-stimulated complex revealed that RAFTK is associated with p190 RhoGAP (p190), RasGAP and ErbB-2, and plays an essential role in mediating the tyrosine phosphorylation of p190 by Src. Mutation of the Src binding site within RAFTK (402) abolished the phosphorylation of p190. In addition, upon HRG stimulation of T47D cells, association of ErbB-2 with RAFTK was observed and found to be indirect and mediated by Src. Expression of wild-type RAFTK (WT) significantly increased MDA-MB-435 and MCF-7 breast cancer cell invasion, while expression of the kinase-mutated RAFTK-R457 (KM) or the Src binding site mutant RAFTK (402) did not affect this cell invasion. Furthermore, HRG leads to the activation of MAP kinase which is mediated by RAFTK. These findings indicate that RAFTK serves as a mediator and an integration point between the GAP proteins and HRG-mediated signaling in breast cancer cells, and implicate RAFTK involvement in the MAP kinase pathway and in breast cancer cell invasion.
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