ArticleThe Journal of biological chemistry2010
Dorsal ruffle microdomains potentiate Met receptor tyrosine kinase signaling and down-regulation.
Article in The Journal of biological chemistry, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers.
What it found
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The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
25 citing papers in PubMed, 45 citations in OpenAlex.
- B cell linker protein (BLNK) is a regulator of Met receptor signaling and trafficking in non-small cell lung cancer.iScience · 2022Article
- Endosomal LC3C-pathway selectively targets plasma membrane cargo for autophagic degradation.Nature communications · 2022Article
- Quantification of ruffle area and dynamics in live or fixed lung adenocarcinoma cells.STAR protocols · 2022Article
- Met-HER3 crosstalk supports proliferation via MPZL3 in MET-amplified cancer cells.Cellular and molecular life sciences : CMLS · 2022Article
- The GAS6-AXL signaling pathway triggers actin remodeling that drives membrane ruffling, macropinocytosis, and cancer-cell invasion.Proceedings of the National Academy of Sciences of the United States of America · 2021Article
- RET isoforms contribute differentially to invasive processes in pancreatic ductal adenocarcinoma.Oncogene · 2020Article
- CLIP-170 spatially modulates receptor tyrosine kinase recycling to coordinate cell migration.Traffic (Copenhagen, Denmark) · 2019Article
- Constitutive and stimulated macropinocytosis in macrophages: roles in immunity and in the pathogenesis of atherosclerosis.Philosophical transactions of the Royal Society of London. Series B, Biological sciences · 2019Review
- HGF-induced migration depends on the PI(3,4,5)PThe Journal of cell biology · 2019Article
- Akt-ing Up Just About Everywhere: Compartment-Specific Akt Activation and Function in Receptor Tyrosine Kinase Signaling.Frontiers in cell and developmental biology · 2019Review
- A RAB35-p85/PI3K axis controls oscillatory apical protrusions required for efficient chemotactic migration.Nature communications · 2018Article
- Identifying ultrasensitive HGF dose-response functions in a 3D mammalian system for synthetic morphogenesis.Scientific reports · 2016Article
- Monocarboxylate transporter 1 contributes to growth factor-induced tumor cell migration independent of transporter activity.Oncotarget · 2016Article
- Article
- Regulation of MET receptor tyrosine kinase signaling by suppressor of cytokine signaling 1 in hepatocellular carcinoma.Oncogene · 2015Article
- c-Met and Other Cell Surface Molecules: Interaction, Activation and Functional Consequences.Biomedicines · 2015Review
- Physiological Signaling and Structure of the HGF Receptor MET.Biomedicines · 2014Review
- Article
- Effects of membrane trafficking on signaling by receptor tyrosine kinases.Cold Spring Harbor perspectives in biology · 2013Review
- Signaling clusters in the cell membrane.Current opinion in cell biology · 2011Review
Corrections and comments
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Authors and funding
4 authors at 2 institutions in 1 country.
Funding
Abstract
Dorsal ruffles are apical protrusions induced in response to many growth factors, yet their function is poorly understood. Here we report that downstream from the hepatocyte growth factor (HGF) receptor tyrosine kinase (RTK), Met, dorsal ruffles function as both a localized signaling microdomain as well as a platform from which the Met RTK internalizes and traffics to a degradative compartment. In response to HGF, colonies of epithelial Madin-Darby canine kidney cells form dorsal ruffles for up to 20 min. Met is transcytosed from the basolateral membrane on Rab4 endosomes, to the apical surface where Met, as well as a Met substrate and scaffold protein, Gab1, localize to the dorsal ruffle membrane. This results in activation of downstream signaling proteins, as evidenced by localization of phospho-ERK1/2 to dorsal ruffles. As dorsal ruffles collapse, Met is internalized into EEA1- and Rab5-positive endosomes and is targeted for degradation through delivery to an Hrs-positive sorting compartment. Enhancing HGF-dependent dorsal ruffle formation, through overexpression of Gab1 or activated Pak1 kinase, promotes more efficient degradation of the Met RTK. Conversely, the ablation of dorsal ruffle formation, by pre-treatment with SITS (4-acetamido-4'-isothiocyabatostilbene-2',2-disulfonic acid) or expression of a Gab1 mutant, impairs Met degradation. Taken together, these data support a function for dorsal ruffles as a biologically relevant signaling microenvironment and a mechanism for Met receptor internalization and degradation.
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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.