ArticleCellular signalling2008
c-Src trafficking and co-localization with the EGF receptor promotes EGF ligand-independent EGF receptor activation and signaling.
Article in Cellular signalling, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 54 papers.
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Who cites it
54 citing papers in PubMed, 87 citations in OpenAlex.
- CDCP1/mitochondrial Src axis increases electron transport chain function to promote metastasis in triple-negative breast cancer.British journal of cancer · 2025Article
- Internalization-related host factors of common respiratory viruses.Frontiers in immunology · 2025Review
- Anti-EGFR aptamer exhibits direct anti-cancer effects in NSCLC cells harboring EGFR L858R mutations.NPJ precision oncology · 2024Article
- Targeting aryl hydrocarbon receptor to prevent cancer in barrier organs.Biochemical pharmacology · 2024Review
- Progesterone receptor potentiates macropinocytosis through CDC42 in pancreatic ductal adenocarcinoma.Oncogenesis · 2024Article
- EGFR trafficking: effect of dimerization, dynamics, and mutation.Frontiers in oncology · 2023Review
- Regulatory Roles of the N-Terminal Intrinsically Disordered Region of Modular Src.International journal of molecular sciences · 2022Review
- Receptors for Respiratory Syncytial Virus Infection and Host Factors Regulating the Life Cycle of Respiratory Syncytial Virus.Frontiers in cellular and infection microbiology · 2022Review
- Toll-like receptor-mediated innate immunity against herpesviridae infection: a current perspective on viral infection signaling pathways.Virology journal · 2020Review
- PAG1 directs SRC-family kinase intracellular localization to mediate receptor tyrosine kinase-induced differentiation.Molecular biology of the cell · 2020Article
- mTOR Inhibition Leads to Src-Mediated EGFR Internalisation and Degradation in Glioma Cells.Cancers · 2020Article
- Epidermal Growth Factor Receptor and Abl2 Kinase Regulate Distinct Steps of Human Papillomavirus 16 Endocytosis.Journal of virology · 2020Article
- Membrane Anchoring of Hck Kinase via the Intrinsically Disordered SH4-U and Length Scale Associated with Subcellular Localization.Journal of molecular biology · 2020Article
- The alpha-1 subunit of the Na+,K+-ATPase (ATP1A1) is required for macropinocytic entry of respiratory syncytial virus (RSV) in human respiratory epithelial cells.PLoS pathogens · 2019Article
- Chemoproteomic Method for Profiling Inhibitor-Bound Kinase Complexes.Journal of the American Chemical Society · 2019Article
- Article
- Src activation by Chk1 promotes actin patch formation and prevents chromatin bridge breakage in cytokinesis.The Journal of cell biology · 2018Article
- Measles Virus Enters Breast and Colon Cancer Cell Lines through a PVRL4-Mediated Macropinocytosis Pathway.Journal of virology · 2017Article
- Unravelling the Mechanism of TrkA-Induced Cell Death by Macropinocytosis in Medulloblastoma Daoy Cells.Molecular and cellular biology · 2016Article
- The regulation of oncogenic Ras/ERK signalling by dual-specificity mitogen activated protein kinase phosphatases (MKPs).Seminars in cell & developmental biology · 2016Review
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Authors and funding
2 authors at 1 institution in 1 country.
Funding
Abstract
c-Src is a non-receptor tyrosine kinase that associates with both the plasma membrane and endosomal compartments. In many human cancers, especially breast cancer, c-Src and the EGF receptor (EGFR) are overexpressed. Dual overexpression of c-Src and EGFR correlates with a Src-dependent increase in activation of EGFR, and synergism between these two tyrosine kinases increases the mitogenic activity of EGFR. Despite extensive studies of the functional interaction between c-Src and EGFR, little is known about the interactions in the trafficking pathways for the two proteins and how that influences signaling. Given the synergism between c-Src and EGFR, and the finding that EGFR is internalized and can signal from endosomes, we hypothesized that c-Src and EGFR traffic together through the endocytic pathway. Here we use a regulatable c-SrcGFP fusion protein that is a bona fide marker for c-Src to show that c-Src undergoes constitutive macropinocytosis from the plasma membrane into endocytic compartments. The movement of c-Src was dependent on its tyrosine kinase activity. Stimulation of cells with EGF revealed that c-Src traffics into the cell with activated EGFR and that c-Src expression and kinase activity prolongs EGFR activation. Surprisingly, even in the absence of EGF addition, c-Src expression induced activation of EGFR and of EGFR-mediated downstream signaling targets ERK and Shc. These data suggest that the synergy between c-Src and EGFR also occurs as these two kinases traffic together, and that their co-localization promotes EGFR-mediated signaling.
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Registered trials
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.