VAV2 regulates epidermal growth factor receptor endocytosis and degradation

Thalappilly, Subhash; Soubeyran, Philippe; Iovanna, Juan; Dusetti, Nelson

doi:10.1038/onc.2010.1

Cited by 36 publications

(34 citation statements)

References 56 publications

(75 reference statements)

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“…As Vav2 has been implicated as an endocytic regulator for various receptors including that of EGF (e.g. Thalappilly et al, 2010), this protein might also associate with clathrin although the threedimensional context in which the motif is presented [it is localised within a calponin homology domain (Tybulewicz, 2005)], could be functionally important.…”

Section: Discussionmentioning

confidence: 99%

SNX15 links clathrin endocytosis to the PtdIns(3)P early endosome independent of the APPL1 endosome

Danson¹,

Brown²,

Hemmings³

et al. 2013

Journal of Cell Science

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SummarySorting nexins (SNXs) are key regulators of the endosomal network. In designing an RNAi-mediated loss-of-function screen, we establish that of 30 human SNXs only SNX3, SNX5, SNX9, SNX15 and SNX21 appear to regulate EGF receptor degradative sorting. Suppression of SNX15 results in a delay in receptor degradation arising from a defect in movement of newly internalised EGF-receptorlabelled vesicles into early endosomes. Besides a phosphatidylinositol 3-phosphate-and PX-domain-dependent association to early endosomes, SNX15 also associates with clathrin-coated pits and clathrin-coated vesicles by direct binding to clathrin through a noncanonical clathrin-binding box. From live-cell imaging, it was identified that the activated EGF receptor enters distinct sub-populations of SNX15-and APPL1-labelled peripheral endocytic vesicles, which do not undergo heterotypic fusion. The SNX15-decorated receptorcontaining sub-population does, however, undergo direct fusion with the Rab5-labelled early endosome. Our data are consistent with a model in which the EGF receptor enters the early endosome following clathrin-mediated endocytosis through at least two parallel pathways: maturation through an APPL1-intermediate compartment and an alternative more direct fusion between SNX15-decorated endocytic vesicles and the Rab5-positive early endosome.

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Section: Discussionmentioning

confidence: 99%

SNX15 links clathrin endocytosis to the PtdIns(3)P early endosome independent of the APPL1 endosome

Danson¹,

Brown²,

Hemmings³

et al. 2013

Journal of Cell Science

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“…5c). Since it had been reported that Vav2 expression affects EGFR endocytosis and degradation 50 , we assessed this for c-Met and found that c-Met degradation ( Supplementary Fig. 11c) and endocytosis ( Supplementary Fig.…”

mentioning

confidence: 99%

Receptor tyrosine kinase c-Met controls the cytoskeleton from different endosomes via different pathways

2014

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Receptor tyrosine kinases (RTKs) are increasingly recognized as having the capacity to signal post-internalization. Signalling outputs and/or duration, and subsequent cellular outcome, are thought to be distinct when emanating from endosomes compared with those from the plasma membrane. Here we show, in invasive, basal-like human breast cell models, that different mechanisms are engaged by the RTK c-Met in two different endosomes to control the actin cytoskeleton via the key migratory signal output Rac1. Despite an acute activation of Rac1 from peripheral endosomes (PEs), c-Met needs to traffic to a perinuclear endosome (PNE) to sustain Rac1 signalling, trigger optimal membrane ruffling, cell migration and invasion. Unexpectedly, in the PNE but not in the PE, PI3K and the Rac-GEF Vav2 are required. Thus we describe a novel endosomal signalling mechanism whereby one signal output, Rac1, is stimulated through distinct pathways by the same RTK depending on which endosome it is localized to in the cell.

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“…This stimulates the phosphorylation of EGFR, ERK and Akt and promotes growth factor-induced cell adhesion, migration, spreading and proliferation [19]. Another gene with a similar regulation pattern was integrin 5 (ITGA5), a subunit of the 51 integrin that is a specific fibronectin receptor and mediates cell attachment, migration, and proliferation in many cells [20]. SDC2 expression was also regulated by MR-1 and can promote Tiam1-dependent Rac activation to promote migration of rectal cancer cells [21].…”

Section: Discussionmentioning

confidence: 99%

Myofibrillogenesis regulator-1 promotes cell adhesion and migration in human hepatoma cells

Zhao

Ren

et al. 2013

Chin. Sci. Bull.

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Myofibrillogenesis regulator-1 (MR-1) is a gene overexpressed usually in many human cancers. However, the effects of MR-1 on cell proliferation, adhesion, migration and genome-wide gene regulation are still unclear. In this study, a human hepatoma cell line that highly overexpresses MR-1, BEL-7402/MR-1 cells was established. While the high expression of MR-1 did not promote cell proliferation, it significantly increased cell spreading, adhesion and migration compared with control cells. A total of 147 genes were regulated by MR-1 expression, 46 genes were down-regulated and 101 genes were up-regulated by MR-1 overexpression. Many of these genes were related to cell adhesion, cytoskeletal regulation, MAPK signaling, and cell cycle related pathways. Western blot analysis further confirmed the regulation of pathways associated with migration by MR-1. These results suggest that MR-1 is involved in the regulation of cancer cell adhesion, migration and related gene expression.

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VAV2 regulates epidermal growth factor receptor endocytosis and degradation

Cited by 36 publications

References 56 publications

SNX15 links clathrin endocytosis to the PtdIns(3)P early endosome independent of the APPL1 endosome

SNX15 links clathrin endocytosis to the PtdIns(3)P early endosome independent of the APPL1 endosome

Receptor tyrosine kinase c-Met controls the cytoskeleton from different endosomes via different pathways

Myofibrillogenesis regulator-1 promotes cell adhesion and migration in human hepatoma cells

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