The Gab1 PH Domain Is Required for Localization of Gab1 at Sites of Cell-Cell Contact and Epithelial Morphogenesis Downstream from the Met Receptor Tyrosine Kinase

Maroun, Christiane R.; Holgado-Madruga, Marina; Royal, Isabelle; Naujokas, Monica A.; Fournier, Tanya M.; Wong, Albert J.; Park, Morag

doi:10.1128/mcb.19.3.1784

Cited by 186 publications

(373 citation statements)

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“…In epithelial cells, Gab1 is the major substrate for the Met RTK (Nguyen et al, 1997), and genetic and cell biological studies (Maroun et al, 1999;Maroun et al, 2000Maroun et al, , 2003 have demonstrated that Gab1 is crucial for the biological responses downstream from Met. Embryos nullizygous for Gab1 display all of the defects observed in Met or HGF/SF null embryos (Itoh et al, 2000;Sachs et al, 2000).…”

Section: Met Signal Transductionmentioning

confidence: 99%

From Tpr-Met to Met, tumorigenesis and tubes

2007

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The receptor for hepatocyte growth factor (HGF)/scatter factor (SF), Met, controls a program of invasive epithelial growth through the coordination of cell proliferation and survival, cell migration and epithelial morphogenesis. This process is important during embryogenesis and for organ regeneration in the adult. However, when deregulated the HGF/SF-Met signaling axis contributes to tumorigenesis and metastasis. Studies on the oncogenic activation of the Met receptor have shed light on the molecular mechanisms underlying the oncogenic activation of receptor tyrosine kinase (RTKs). More than a decade ago, work on the Met related oncogene, Tpr-Met, revealed the mechanism for activation of RTK-derived oncogenes generated following chromosomal translocation. More recently, studies on the mechanisms of downregulation of the Met RTK highlight a role for loss of downregulation in RTK oncogenic activation.

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Section: Met Signal Transductionmentioning

confidence: 99%

From Tpr-Met to Met, tumorigenesis and tubes

2007

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“…1). As a whole, this apparatus leads to efficient activation of downstream signal transduction pathways that include the mitogenactivated protein kinase (MAPK) cascades (extracellular signal-regulated kinase 1 (ERK1) and ERK2, Jun amino-terminal kinases (JNKs) and p38), the phosphoinositide 3-kinase-Akt (PI3K-Akt) axis, signal transducer and activator of transcription proteins (STATs), and the nuclear factor-κB inhibitor-α (IκBα)-nuclear factor-κB (NF-κB) complex 22,25,42,43,44 . All of these pathways positively control MET-dependent cell proliferation, survival and migration.…”

Section: Introductionmentioning

confidence: 99%

“…The promiscuous docking motif in the C-terminal tail of MET binds numerous Src-homology-2 domain (SH2 domain)-containing effectors, such as PI3K 37 , the non-receptor tyrosine kinase Src 37 , the growth factor receptor-bound protein 2 (GRB2) and SH2 domain-containing transforming protein (SHC) adaptors 37,45,46 , SHP2 (also known as PTPN11; an upstream activator of Src and Ras) 46 , phospholipase Cγ1 (PLCγ1) 37 and the transcription factor STAT3 (Refs 47,48). MET also associates with GRB2-associated-binding protein 1 (GAB1), a multi-adaptor protein that, upon phosphorylation by the MET receptor, provides extra binding sites for SHC, PI3K, SHP2, CRK, PLCγ1 and p120 Ras-GTPase-activating protein (p120-Ras-GAP) 43,44,49,50,51,52,53 . The association between MET and GAB1 occurs directly, through a unique 13-amino-acid MET binding site (MBS) on GAB1, and indirectly, through MET-bound GRB2 (Refs 51,54).…”

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confidence: 99%

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

Trusolino

Bertotti

Comoglio

2010

Nat Rev Mol Cell Biol

1,061

1,076

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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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“…An additional role in cell survival has been reported [14,15]. In hepatocytes, PtdIns 3-kinase contributes to the regulation of several biological functions, including EGF-induced and insulininduced mitogenesis [16], insulin-induced [17] and HGF-induced [18] morphogenesis, insulin-dependent inhibition of apolipoprotein B secretion [19] and autophagy [20]. PtdIns 3-kinase is a lipid (and serine) kinase capable of phosphorylating phosphatidylinositol (PtdIns), PtdIns(4)P and PtdIns(4,5)P 2 to produce PtdIns(3)P, PtdIns(3,4)P 2 and PtdIns(3,4,5)P 3 , respectively, although the major product in vivo is PtdIns(3,4,5)P 3 (reviewed in [21,22]).…”

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confidence: 99%

“…These IRS families are currently known to be phosphorylated on tyrosine residues upon stimulation of receptors other than those for insulin or IGF-I. They include receptors possessing tyrosine kinase domains, such as those for hepatocyte growth factor (HGF) [18] and brain-derived neurotrophic factor [30], and receptors lacking intrinsic tyrosine kinase activity, such as those belonging to the cytokine/hematopoietin receptor superfamily (for example, the receptors for growth hormone, prolactin, angiotensin, interleukins and interferons; reviewed in [31]). There was no definite evidence, however, for the involvement of EGF in the phosphorylation of IRS-1 or IRS-2 in any cell types, as reviewed in 1996 [32].…”

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confidence: 99%

Involvement of insulin receptor substrates in epidermal growth factor induced activation of phosphatidylinositol 3‐kinase in rat hepatocyte primary culture

Fujioka

2001

European Journal of Biochemistry

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Short-term incubation of adult rat hepatocytes with epidermal growth factor (EGF) caused tyrosine phosphorylation of insulin receptor substrate (IRS)-1 and IRS-2 when the cells had been submitted to primary culture from 1±18 h. Tyrosine-phosphorylated IRS-1 and IRS-2 bound to the regulatory subunit (p85) of phosphatidylinositol (PtdIns) 3-kinase, thereby activating the enzymic activity. Tyrosine phosphorylation of the IRSs and activation of PtdIns 3-kinase in 3 h cultured hepatocytes both proceeded similarly to the same actions of insulin; the activation was rapid and transient, with peak values at 15±30 s and with similar EC 50 s in the nm range in both cases. A possible involvement of insulin receptors in these insulin-like actions of EGF was excluded by the following three lines of evidence. Insulin caused tyrosine phosphorylation of the insulin receptor b-subunit but EGF did not. In contrast, the EGF receptor was phosphorylated by EGF, but the insulin receptor was not. The actions of EGF, but not those of insulin, were inhibited by AG1478, a selective inhibitor of EGF receptor tyrosine kinase. Cultured hepatocytes exposed to insulin or insulin-like growth factor-I (IGF-I) for a short period responded to the subsequent addition of EGF, whereas EGF-treated cells responded to insulin. The cells, however, displayed receptor desensitization under the same conditions, that is, no response was observed upon repeated addition of the same agonist, EGF, insulin or IGF-I. Thus, the EGF receptor-initiated signalling was mediated by PtdIns 3-kinase associated with tyrosine-phosphorylated IRSs in short-term cultured rat hepatocytes.Keywords: signal transduction; tyrosine kinase receptor; tyrosine phosphorylation.Membrane receptors having intrinsic protein tyrosine kinase activity are known to be responsible for promoting proliferation of hepatocytes [1] as well as many other types of cells [2]. If kept in a serum-free medium, DNA synthesis in hepatocytes occurs with the addition of growth factors, among which epidermal growth factor (EGF) is effective in vivo and in culture [3,4] as a result of its binding to typical tyrosine kinase related receptors. The EGF receptor (EGFR) is the prototype of the type I ErbB subfamily, which includes three additional members, ErbB-2/Neu, ErbB3 and ErbB4 [5]. All members of the ErbB subfamily have a domain that serves as a docking site for specific SH-2 domains, which are present in signalling proteins such as the p85 regulatory subunit of phosphatidylinositol (PtdIns) 3-kinase. EGF has been shown to activate PtdIns 3-kinase, although it does not bind directly to the EGFR but is instead activated via association with p120 cbl [6,7] or Gab1 [8], which are phosphorylated on tyrosine residues by the growth factor. PtdIns 3-kinase may also interact with heterodimers of other members of the EGFR family, such as ErbB3, in response to EGF [9,10].PtdIns 3-kinase plays important roles in a wide variety of biological responses to hormones, growth factors and cytokines [11]. The typical responses s...

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The Gab1 PH Domain Is Required for Localization of Gab1 at Sites of Cell-Cell Contact and Epithelial Morphogenesis Downstream from the Met Receptor Tyrosine Kinase

Cited by 186 publications

References 74 publications

From Tpr-Met to Met, tumorigenesis and tubes

From Tpr-Met to Met, tumorigenesis and tubes

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

Involvement of insulin receptor substrates in epidermal growth factor induced activation of phosphatidylinositol 3‐kinase in rat hepatocyte primary culture

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