Scatter factor and hepatocyte growth factor are indistinguishable ligands for the MET receptor.

Naldini, Luigi; Weidner, K. Michael; Vigna, Elisa; Gaudino, Giovanni; Bardelli, Alberto; Ponzetto, Carola; Narsimhan, Radha P.; Hartmann, Guido; Zarnegar, Reza; Michalopoulos, George K.

doi:10.1002/j.1460-2075.1991.tb07836.x

Cited by 661 publications

(435 citation statements)

References 45 publications

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“…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). MET function is required for various morphogenetic events in both embryonic and adult life 21,22 and it drives the malignant progression of several different types of tumours 23 .…”

Section: Introductionmentioning

confidence: 99%

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

Trusolino

Bertotti

Comoglio

2010

Nat Rev Mol Cell Biol

1,040

1,061

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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). ...

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Section: Introductionmentioning

confidence: 99%

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

Trusolino

Bertotti

Comoglio

2010

Nat Rev Mol Cell Biol

1,040

1,061

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“…Hepatocyte growth factor (HGF) or scatter factor, is a multifunctional peptide that signals via Met, a tyrosine kinase receptor, which undergoes tyrosine phosphorylation and activation [1][2][3]. In turn, the signal is transduced downstream, either directly or through its adaptor molecules-Gab1 or Grb2, which trigger activation of signaling such as ERK1/2/MAPK, PLC-γ, PI3K, SHP2 and others [4][5][6][7][8][9].…”

Section: Introductionmentioning

confidence: 99%

Tyrosine residues 654 and 670 in β-catenin are crucial in regulation of Met–β-catenin interactions

Zeng

Apte

Micsenyi

et al. 2006

Experimental Cell Research

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Abstractβ-Catenin, a key component of the canonical Wnt pathway is also regulated by tyrosine phosphorylation that regulates its association to E-cadherin. Previously, we reported its association with the hepatocyte growth factor (HGF) receptor-Met, at the membrane. HGF induced met-β-catenin dissociation and nuclear translocation of β-catenin, which was tyrosine-phosphorylation dependent. Here, we further investigate the met-β-catenin interaction, by selectively mutating several tyrosine residues alone or in combination, in β-catenin. The mutants were subcloned into FLAG-CMV vector & stably transfected into rat hepatoma cells, which were treated with HGF. All single or double mutant-transfected cells continued to show HGF induced nuclear translocation of FLAG-β-catenin except the mutations affecting 654 and 670 simultaneously (Y654/670F), which coincided with the lack of formation of β-catenin-TCF complex and DNA synthesis, in response to the HGF treatment. In addition, the Y654/670F-transfected cells also showed no phosphorylation of β-catenin or dissociation from Met in response to HGF. Thus, intact 654 and 670 tyrosine residues in β-catenin are crucial in HGF-mediated β-catenin translocation, activation, and mitogenesis.

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“…HGF stimulates the endothelial cells to elaborate Immunoprecipitates were resolved on SDS ± PAGE, and proteins were visualized by autoradiography Oncogene (2000) 19, 124 ± 133 ã 2000 Macmillan Publishers Ltd All rights reserved 0950 ± 9232/00 $15.00 www.nature.com/onc proteases, degrade the extracellular matrix, migrate and proliferate (Bussolino et al, 1992). The biological responses mediated by the HGF receptor, which is encoded by the proto-oncogene Met, (Naldini et al, 1991) are triggered by the tyrosine phosphorylation of a single multifunctional docking site located in the receptor's carboxyterminal tail (Ponzetto et al, 1994); this sequence interacts with several cytoplasmic transducers (Ponzetto et al, 1994;Pelicci et al, 1995;Weidner et al, 1996) either directly or indirectly.…”

Section: Introductionmentioning

confidence: 99%

Transforming Growth Factor β2 inhibition of Hepatocyte Growth Factor-induced endothelial proliferation and migration

Manganini

Maier

2000

Oncogene

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Angiogenesis is a highly controlled event which depends on the proper equilibrium of activators and inhibitors present within the microenvironment. Hepatocyte Growth Factor (HGF) activates migration and proliferation of endothelial cells and is angiogenic, acting through the tyrosine kinase receptor encoded by the Met protooncogene. To get insights into the molecular mechanisms involved in HGF-induced angiogenesis, we searched for cDNAs di erentially expressed in human endothelial cells exposed to HGF, a potent angiogenic factor. We found that HGF-treated endothelial cells upregulated the expression of Transforming Growth Factor (TGF) b 2 . To understand the signi®cance of this ®nding, we cultured endothelial cells with HGF and TGF b 2 simultaneously. We found that TGF b 2 impairs HGFdependent proliferative and migratory responses. TGF b 2 did not prevent the tyrosine phosphorylation of Met, but it inhibited some signalling pathways activated by HGF. We show that endothelial proliferation induced by HGF required the activation of the MAPK cascade, while HGF-induced endothelial migration was dependent on the tyrosine phosphorylation of Src. Indeed, TGF b 2 inhibited HGF e ects because it prevented HGF-induced MAP kinase activation and tyrosine phosphorylation of Src. We suggest that the induction of TGF b 2 by HGF in endothelial cells may represent a physiologic mechanism to counterbalance HGF angiogenic activity. Oncogene (2000) 19, 124 ± 133.

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Scatter factor and hepatocyte growth factor are indistinguishable ligands for the MET receptor.

Cited by 661 publications

References 45 publications

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

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

Tyrosine residues 654 and 670 in β-catenin are crucial in regulation of Met–β-catenin interactions

Transforming Growth Factor β2 inhibition of Hepatocyte Growth Factor-induced endothelial proliferation and migration

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