Molecular ticket to enter cells

Oved, Shlomo; Yarden, Yosef

doi:10.1038/416133a

Cited by 46 publications

(31 citation statements)

References 8 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…23), whereas Rb was downregulated. By contrast, the transcription of Cbl, endophilin, and ubiquitin genes, which are related to the HER-2/neu degradation pathway (41), is downregulated in wk22nt in comparison with wk22pb mammary glands.…”

Section: Figurementioning

confidence: 87%

Concordant morphologic and gene expression data show that a vaccine halts HER-2/neu preneoplastic lesions

Quaglino¹,

Rolla²,

Iezzi³

et al. 2004

J. Clin. Invest.

View full text Add to dashboard Cite

While much experimental data shows that vaccination efficiently inhibits a subsequent challenge by a transplantable tumor, its ability to inhibit the progress of autochthonous preneoplastic lesions is virtually unknown. In this article, we show that a combined DNA and cell vaccine persistently inhibits such lesions in a murine HER-2/neu mammary carcinogenesis model. At 10 weeks of age, all of the ten mammary gland samples from HER-2/neu–transgenic mice displayed foci of hyperplasia that progressed to invasive tumors. Vaccination with plasmids coding for the transmembrane and extracellular domain of rat p185neu followed by a boost with rp185neu+ allogeneic cells secreting IFN-γ kept 48% of mice tumor free. At 22 weeks, their mammary glands were indistinguishable from those of 10-week-old untreated mice. Furthermore, the transcription patterns of the two sets of glands coincided. Of the 12,000 genes analyzed, 17 were differentially expressed and related to the antibody response. The use of B cell knockout mice as well as the concordance of morphologic and gene expression data demonstrated that the Ab response is the main mechanism facilitating tumor growth arrest. This finding suggests that a new way can be found to secure the immunologic control of the progression of HER-2/neu preneoplastic lesions

show abstract

Section: Figurementioning

confidence: 87%

Concordant morphologic and gene expression data show that a vaccine halts HER-2/neu preneoplastic lesions

Quaglino¹,

Rolla²,

Iezzi³

et al. 2004

J. Clin. Invest.

View full text Add to dashboard Cite

show abstract

“…Many receptors, including PDFGR, nerve growth factor receptor and hepatocyte growth factor receptor, are dimerized and internalized after ligand binding (Oved and Yarden, 2002;Schlessinger, 2002). Thus, it is possible that our findings for ErbB receptors are also applicable to these receptor tyrosine kinases.…”

Section: Research Articlementioning

confidence: 90%

Dimerization drives EGF receptor endocytosis through two sets of compatible endocytic codes

Wang

Chen

Wang

2015

Journal of Cell Science

View full text Add to dashboard Cite

We have shown previously that epidermal growth factor (EGF) receptor (EGFR) endocytosis is controlled by EGFR dimerization. However, it is not clear how the dimerization drives receptor internalization. We propose that EGFR endocytosis is driven by dimerization, bringing two sets of endocytic codes, one contained in each receptor monomer, in close proximity. Here, we tested this hypothesis by generating specific homo-or hetero-dimers of various receptors and their mutants. We show that ErbB2 and ErbB3 homodimers are endocytosis deficient owing to the lack of endocytic codes. Interestingly, EGFR-ErbB2 or EGFR-ErbB3 heterodimers are also endocytosis deficient. Moreover, the heterodimer of EGFR and the endocytosis-deficient mutant EGFRD1005-1017 is also impaired in endocytosis. These results indicate that two sets of endocytic codes are required for receptor endocytosis. We found that an EGFR-PDGFRb heterodimer is endocytosis deficient, although both EGFR and PDGFRb homodimers are endocytosiscompetent, indicating that two compatible sets of endocytic codes are required. Finally, we found that to mediate the endocytosis of the receptor dimer, the two sets of compatible endocytic codes, one contained in each receptor molecule, have to be spatially coordinated.

show abstract

“…Seemingly active MET is not polyubiquitylated, and is therefore unlikely to be targeted for degradation by theproteasome 87 ; however, proteasomal destruction of MET can occur in an ubiquitin-independent manner (see below). CBL also attracts -through the scaffold molecule CBL-interacting protein 85 (CIN85; also known as SH3KBP1) -endophilins, a family of proteins that assist the negative curvature, invagination and scission of the planar plasma membrane during the early phases of endocytosis 90 . Therefore, CBL promotes the physical internalization of MET while tagging it for lysosomal degradation 91 (Fig.…”

Section: Regulation Of Met Signallingmentioning

confidence: 99%

MET signalling: principles and functions in development, organ regeneration and cancer

Trusolino

Bertotti

Comoglio

2010

Nat Rev Mol Cell Biol

1,083

1,076

View full text Add to dashboard Cite

The MET tyrosine kinase receptor (also known as the HGF receptor) promotes tissue remodelling, which underlies developmental morphogenesis, wound repair, organ homeostasis and cancer metastasis, by integrating growth, survival and migration cues in response to environmental stimuli or cell-autonomous perturbations. The versatility of MET-mediated biological responses is sustained by qualitative and quantitative signal modulation. Qualitative mechanisms include the engagement of dedicated signal transducers and the subcellular compartmentalization of MET signalling pathways, whereas quantitative regulation involves MET partnering with adaptor amplifiers or being degraded through the shedding of its extracellular domain or through intracellular ubiquitylation. Controlled activation of MET signalling can be exploited in regenerative medicine, whereas MET inhibition might slow down tumour progression.Throughout embryogenesis, cells bud off from developing tissues and move outwards to shape and pattern the complex architecture of prospective organs 1 . A similar process occurs in adult life during wound healing and tissue repair, when lingering cells migrate into injury sites to recreate the pre-existing structures 2 . The acquisition of cell motility is necessary, but not sufficient, for this event. Cells that detach from their neighbours must elude anoikis, a form of apoptotic cell death that occurs when cells lose adhesion with the extracellular matrix 3 . Moreover, migratory cells undergo extensive mitotic divisions to produce 'founder populations', which settle in newly forming organs during development or colonize worn tissues during repair 4,5 . The normal phases of embryogenesis and organ regeneration strongly resemble the pathological process of tumour invasiveness: similarly to cells at the wound edge, cells at the tumour's leading front disrupt intercellular contacts and infiltrate the adjacent surroundings, where they resist anoikis and grow before lodging in the blood vessels for systemic dissemination 6 . This resemblance is not simply a biological correlate, it has a common mechanistic basis: cancer cells resurrect the latent schemes of cellular reorganization, which are usually confined to embryonic development and damaged adult organs, and leverage them to become competent for metastasization 7 . The activities -motility, survival and proliferation -that occur in developing, injured and neoplastic tissues embody a biological programme that is defined as 'invasive growth' 8 . This is triggered by extracellular stimuli that regulate the activity of several transcription factors that, in turn, modulate the expression of a number of proteins, ranging from cytoskeletal and cell-cell junctional components to cell cycle regulators and anti-apoptotic effectors 9, 10 . One major environmental inducer of invasive growth is hepatocyte growth factor (HGF, also known as scatter factor), the ligand for the MET tyrosine kinase receptor (also known as the HGF receptor) 11,12,13,14,15,16,17,18,19,20 (Box 1). ...

show abstract

Molecular ticket to enter cells

Cited by 46 publications

References 8 publications

Concordant morphologic and gene expression data show that a vaccine halts HER-2/neu preneoplastic lesions

Concordant morphologic and gene expression data show that a vaccine halts HER-2/neu preneoplastic lesions

Dimerization drives EGF receptor endocytosis through two sets of compatible endocytic codes

MET signalling: principles and functions in development, organ regeneration and cancer

Contact Info

Product

Resources

About