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EGFR — TGFA

Pathways - manually collected, often from reviews:

• OpenBEL Selventa BEL large corpus: Complex of EGF-EGFR → TGFA (decreases)
  Evidence: HB-EGF and TGFA, although immunologically distinct from EGF, reportedly inhibit the binding of EGF to its own receptor
• OpenBEL Selventa BEL large corpus: Complex of EGFR-EGFR → TGFA (directlyIncreases)
  Evidence: Figure 1 , ERBB receptors, ligands, dimers and downstream signalling pathways. a , Members of the epidermal growth factor (EGF) family of growth factors are ligands for the ERBB receptors. Ligand binding to ERBB receptors induces the formation of receptor homo- and heterodimers and the activation of the intrinsic kinase domain, resulting in phosphorylation on specific tyrosine residues within the cytoplasmic tail. These phosphorylated residues serve as docking sites for a range of proteins, the ...
• OpenBEL Selventa BEL large corpus: EGFR → TGFA (increases) Darmoul et al., Mol Cancer Res 2004*
  Evidence: TGF-alpha directly binds to the EGF receptor and activates it by tyrosine phosphorylation.
• OpenBEL Selventa BEL large corpus: EGFR → TGFA (directlyIncreases, TGFA Activity) Koff et al., Am J Physiol Lung Cell Mol Physiol 2008*
  Evidence: In an airway epithelial cell line (NCI-H292), TNF-alpha-converting enzyme (TACE) small interfering RNA (siRNA) was used to confirm that TACE is the MP involved in TLR (2,3,5,6)-ligand-induced IL-8 and VEGF production. We show that transforming growth factor (TGF)-alpha is the EGFR ligand in this signaling cascade by using TGF-alpha neutralizing antibody and by showing that epithelial production of TGF-alpha occurs in response to TLR ligands.
• OpenBEL Selventa BEL large corpus: EGFR → TGFA (increases, TGFA Translocation)
  Evidence: In a recent article, using an orthotopic mouse tumor model, it was shown that TGF-alpha-expressing tumor cells directly induced ErbB1 expression in ECs; ECs associated with tumors that did not express this ligand were essentially devoid of ErbB1 [109].
• OpenBEL Selventa BEL large corpus: EGFR → Complex of EGFR-TGFA (directlyIncreases, EGFR/TGFA Activity)
  Evidence: Several growth factors, most notably insulin-like growth factor-2 (IGF2) and transforming growth factor-a (TGF-a), are also HIF-1 target genes. Binding of these factors to their cognate receptors the insulin-like growth factor 1 receptor (IGF1R) and epidermal growth-factor receptor (EGFR), respectively activates signal-transduction pathways that lead both to HIF-1a expression (as described above) and to cell proliferation survival. HIF-1 therefore contributes to autocrine-signalling pathways tha...
• OpenBEL Selventa BEL large corpus: EGFR → Complex of EGFR-TGFA (directlyIncreases, EGFR/TGFA Activity)
  Evidence: Depsipeptide Depsipeptide was originally isolated from a strain of Chromobacterium violaceum. Initial studies with this bicyclic peptide demonstrated a selective decrease in c-myc expression. However, growth inhibition of the Ha-rastransformed NIH-3T3 clonal cell line Ras-1 was also observed in the absence of altered Ha-ras mRNA expression [67]. Depsipeptide appears to regulate the cell cycle at several points, including cell cycle arrest at G0/G1 and inhibition of signal transduction through mi...
• KEGG Pathways in cancer: TGFA → EGFR (protein-protein, activation)
• KEGG ErbB signaling pathway: TGFA → Complex of EGFR (protein-protein, activation)
• KEGG ErbB signaling pathway: TGFA → EGFR (protein-protein, activation)
• KEGG Pancreatic cancer: TGFA → EGFR (protein-protein, activation)
• KEGG Glioma: TGFA → EGFR (protein-protein, activation)
• KEGG Glioma: TGFA → EGFR (protein-protein, activation)
• KEGG Prostate cancer: EGF/IGF1/INS/PDGFA/PDGFB/PDGFC/PDGFD/TGFA → EGFR/ERBB2/FGFR1/FGFR2/IGF1R/INSRR/PDGFRA/PDGFRB (protein-protein, activation)
  
• KEGG Non-small cell lung cancer: TGFA → EGFR (protein-protein, activation)
• NCI Pathway Database ErbB receptor signaling network: EGFR/ErbB3/TGFA complex (EGFR-ERBB3-TGFA) → EGFR (EGFR) (modification, collaborate) Riese et al., J Biol Chem 1996
  Evidence: assay, physical interaction
• NCI Pathway Database ErbB receptor signaling network: EGFR/ErbB3/TGFA complex (EGFR-ERBB3-TGFA) → ErbB3 (ERBB3) (modification, collaborate) Riese et al., J Biol Chem 1996
  Evidence: assay, physical interaction
• NCI Pathway Database ErbB receptor signaling network: EGFR/ErbB3/TGFA complex (EGFR-ERBB3-TGFA) → TGFA (TGFA) (modification, collaborate) Riese et al., J Biol Chem 1996
  Evidence: assay, physical interaction
• NCI Pathway Database ErbB receptor signaling network: EGFR (EGFR) → TGFA (TGFA) (modification, collaborate) Riese et al., J Biol Chem 1996
  Evidence: assay, physical interaction
• NCI Pathway Database ErbB receptor signaling network: EGFR (EGFR) → TGFA (TGFA) (modification, collaborate) Todaro et al., Proc Natl Acad Sci U S A 1980*, Reynolds et al., Nature 1981*, Massagué et al., J Biol Chem 1983*, Riese et al., J Biol Chem 1996
  Evidence: assay, physical interaction
• NCI Pathway Database ErbB receptor signaling network: EGFR (EGFR) → EGFR/EGFR/TGFA/TGFA complex (EGFR-TGFA) (modification, collaborate)
  Todaro et al., Proc Natl Acad Sci U S A 1980*, Reynolds et al., Nature 1981*, Massagué et al., J Biol Chem 1983*, Riese et al., J Biol Chem 1996
  Evidence: assay, physical interaction
• NCI Pathway Database ErbB receptor signaling network: TGFA (TGFA) → EGFR/EGFR/TGFA/TGFA complex (EGFR-TGFA) (modification, collaborate)
  Todaro et al., Proc Natl Acad Sci U S A 1980*, Reynolds et al., Nature 1981*, Massagué et al., J Biol Chem 1983*, Riese et al., J Biol Chem 1996
  Evidence: assay, physical interaction
• NCI Pathway Database ErbB receptor signaling network: EGFR/ErbB2/TGFA complex (EGFR-ERBB2-TGFA) → EGFR (EGFR) (modification, collaborate) Riese et al., J Biol Chem 1996
  Evidence: assay, physical interaction
• NCI Pathway Database ErbB receptor signaling network: EGFR/ErbB2/TGFA complex (EGFR-ERBB2-TGFA) → TGFA (TGFA) (modification, collaborate) Riese et al., J Biol Chem 1996
  Evidence: assay, physical interaction
• NCI Pathway Database ErbB receptor signaling network: EGFR/ErbB2/TGFA complex (EGFR-ERBB2-TGFA) → ErbB2 (ERBB2) (modification, collaborate) Riese et al., J Biol Chem 1996
  Evidence: assay, physical interaction
• NCI Pathway Database ErbB receptor signaling network: EGFR (EGFR) → TGFA (TGFA) (modification, collaborate) Riese et al., J Biol Chem 1996
  Evidence: assay, physical interaction
• WikiPathways ErbB Signaling Pathway: TGFA → EGFR (activation)
• WikiPathways Association Between Physico-Chemical Features and Toxicity Associated Pathways: TGFA → EGFR (activation)
• WikiPathways BMP Signaling Pathway in Eyelid Development: TGFA → EGFR (activation)

Protein-Protein interactions - manually collected from original source literature:

Studies that report less than 10 interactions are marked with *

• IRef Bind Interaction: TGFA — EGFR Garrett et al., Cell 2002*
• IRef Bind_translation Interaction: TGFA — EGFR (x-ray crystallography) Garrett et al., Cell 2002*
• IRef Biogrid Interaction: EGFR — TGFA (association, x-ray crystallography) Garrett et al., Cell 2002*
• IRef Dip Interaction: EGFR — TGFA (physical association, biochemical) Puddicombe et al., J Biol Chem 1996*
• IRef Dip Interaction: EGFR — TGFA (physical association, biophysical) McInnes et al., Protein Eng 2000*
• IRef Hprd Interaction: EGFR — TGFA (in vitro) Garrett et al., Cell 2002*
• IRef Intact Interaction: EGFR — TGFA (direct interaction, x-ray crystallography) Garrett et al., Cell 2002*
• IRef Ophid Interaction: EGFR — TGFA (aggregation, interologs mapping) Brown et al., Bioinformatics 2005

Text-mined interactions from Literome

Dent et al., Mol Biol Cell 1999 (Breast Neoplasms...) : Radiation induced release of transforming growth factor alpha activates the epidermal growth factor receptor and mitogen activated protein kinase pathway in carcinoma cells, leading to increased proliferation and protection from radiation induced cell death
Powell et al., Br J Dermatol 1999 (Psoriasis) : Among factors which may be related to hyperplasia of psoriatic keratinocytes is the persistent autocrine stimulation of the epidermal growth factor receptor (EGFR) by transforming growth factor-alpha
Blaudschun et al., FEBS Lett 2000 : The first VEGF peak occurred on mRNA level at 1 h and on protein level at 4 h postirradiation and is fully mediated by the UVB dependent phosphorylation of the epidermal growth factor receptor , which subsequent to its phosphorylation also initiates at least in part the synthesis of transforming growth factor alpha that confers as shown previously the second late VEGF peak at 8 h on mRNA and at 24 h on protein level
Yamanaka et al., Biochem Biophys Res Commun 2001 : Among four EGF-receptor (EGFR) family members, the EGFR was solely activated by EGF, heparin binding EGF (HB-EGF), transforming growth factor alpha ( TGF alpha ), epiregulin (ER), and betacellulin (BTC), resulting in induction of phenotypic modulation of SMCs
Moroni et al., Clin Cancer Res 2001 (Germinoma...) : The goal of this work was to study the expression of epidermal growth factor receptor ( by use of monoclonal antibody EGFR 1 ) and HER-2/neu ( by use of monoclonal antibody EGFR 2 ), as well as EGFR activation [ phosphorylated EGFR ( P-EGFR ) ] and autocrine stimulation [ ligand transforming growth factor-alpha ( TGF-alpha ) ] markers in a series of 24 testicular tumors [ 18 nonseminomatous germ cell tumors ( GCTs ), 1 Leydig cell tumor, and 5 seminomatous GCTs ]
Stortelers et al., Biochemistry 2002 : Epidermal growth factor (EGF) and transforming growth factor (TGF)-alpha are potent activators of the ErbB-1 receptor, but, unlike TGF-alpha, EGF is also a weak activator of ErbB-2/ErbB-3 heterodimers
Xiao et al., Am J Physiol Gastrointest Liver Physiol 2003 : The primary objective of this investigation was to determine the role of signaling pathways initiated by EGFR in regulating the transforming growth factor-alpha ( TGF-alpha ) -induced activation of AP-1 in the gastric mucosa in aged rats
Korc et al., J Clin Invest 1992 (Pancreatic Neoplasms) : The epidermal growth factor (EGF) receptor is activated by both EGF and transforming growth factor-alpha ( TGF-alpha )
Harbers et al., Carcinogenesis 1992 (Adrenal Gland Neoplasms...) : Promotion of ` initiated ' JB6 epidermal cells to the tumor phenotype can be effected by 12-O-tetradecanoylphorbol-13-acetate treatment, by stimulation of epidermal growth factor (EGF) receptor activity with EGF or transforming growth factor alpha and by exposure to the isoquinoline derivative H7
Koon et al., J Biol Chem 2004 : Pretreatment with antibodies against potential EGFR ligands suggested that transforming growth factor-alpha ( TGFalpha ), but not the other EGFR ligands EGF, heparin binding EGF, or amphiregulin, mediates SP-induced EGFR transactivation
Marciniak et al., Mol Cancer Ther 2004 (Prostatic Neoplasms) : The transforming growth factor-alpha induced stimulation of cell growth and activation of EGFR was also inhibited by ERRP
Gordon-Thomson et al., Melanoma Res 2005 (Melanoma) : Epidermal growth factor receptor (EGFR) activation by transforming growth factor alpha ( TGFalpha ) has been implicated in autocrine growth in melanoma, but does not alter melanocyte proliferation
Na et al., Gastroenterology 2005 : By using neutralizing antibodies against known ligands of EGFR, we found that the activation of EGFR and ERK1/2 phosphorylation was mediated by transforming growth factor-alpha ( TGF-alpha )
Zhou et al., Cancer Res 2005 (Adenocarcinoma...) : Previous studies have shown that constitutive activation of epidermal growth factor receptor (EGFR) and ErbB2 by elevated autocrine transforming growth factor-alpha ( TGF-alpha ) expression plays an important role in colon cancer progression
Yamachika et al., Pathol Int 2005 (Adenocarcinoma, Mucinous...) : They expressed epidermal growth factor (EGF) receptor and HER2 on their surface and accordingly, their growth was significantly stimulated by EGF, transforming growth factor (TGF)-alpha and heregulin
Namba et al., Mol Cell Neurosci 2006 : Subchronic stimulation of ErbB1 with transforming growth factor alpha ( TGFalpha ), EGF, or heparin binding EGF (HB-EGF) down-regulated protein expression of the GluR1 AMPA receptor subunit in cultured neocortical neurons
Kumar et al., Mol Cell Biol 1991 (Breast Neoplasms) : Phosphorylation of p185HER2 in the presence of newborn calf serum was not attributable to stimulation of the epidermal growth factor receptor by epidermal growth factor or by transforming growth factor-alpha
Fernandez-Pol et al., Crit Rev Oncog 1991 (Breast Neoplasms) : I summarize some new results on the role of epidermal growth factor (EGF), transforming growth factor (TGF) alpha , and TGF beta in the control of EGF-R protooncogene expression in human breast carcinoma cells
Humphrey et al., Biochem Biophys Res Commun 1991 (Chromosome Deletion...) : EGF and transforming growth factor-a (TGF-a) bound to the mutant EGFR with high affinity and enhanced the intrinsic mutant EGFR kinase activity
Rajput et al., Cancer Res 2007 (Colonic Neoplasms...) : We show that constitutive expression of transforming growth factor-alpha and its subsequent constitutive activation of EGFR allows for cancer cell survival in response to environmental stress in vitro and in vivo as well
McCole et al., J Biol Chem 2007 : We have previously shown that EGFR negatively regulates epithelial chloride secretion as a result of transforming growth factor-alpha mediated EGFR transactivation in response to muscarinic GPCR activation
Charalambous et al., Carcinogenesis 2007 (Neoplasms) : Epidermal growth factor receptor (EGFR) ligands ( transforming growth factor alpha ( TGFalpha ), heparin binding EGF-like growth factor and epiregulin ) are constitutively induced by LMP1, leading to EGFR phosphorylation but also down-regulation, degradation or turn-over, with the appearance of cleaved EGFR fragments
Baldys et al., Biochemistry 2009 : The intracellular processing of the epidermal growth factor receptor (EGFR) induced by epidermal growth factor (EGF) and transforming growth factor-alpha ( TGF-alpha ) has been studied meticulously, with the former resulting in EGFR degradation and the latter in EGFR recycling to the plasma membrane
Peltola et al., Neoplasia (New York, N.Y.) 2009 (Carcinoma, Squamous Cell...) : When directly testing EGFR dependence of Pim-1 expression, up-regulation and nuclear translocation of Pim-1 could be induced through stimulation of EGFR with its ligands EGF or transforming growth factor alpha
Fernandez-Pol et al., J Cell Biochem 1989 (Breast Neoplasms) : Modulation of transforming growth factor alpha dependent expression of epidermal growth factor receptor gene by transforming growth factor beta, triiodothyronine, and retinoic acid
Robertson et al., Surg Oncol 1994 (Precancerous Conditions...) : Autocrine stimulation of EGFr by TGFa or other unrecognized factors may be present in CaP
Jiang et al., Proc Natl Acad Sci U S A 1993 : We have analyzed the effects of EGFR activation on keratin gene transcription by transfecting DNAs containing keratin promoters linked to a reporter gene into primary cultures of human epidermal keratinocytes in the presence or absence of EGF or transforming growth factor alpha ( TGF alpha ), two growth factors that activate EGFR
Adachi et al., Endocrinology 1995 (Leiomyoma...) : Estrogen induces epidermal growth factor (EGF) receptor and its ligands in human fallopian tube : involvement of EGF but not transforming growth factor-alpha in estrogen induced tubal cell growth in vitro
Dlugosz et al., Cancer Res 1995 (Cell Transformation, Neoplastic...) : Autocrine epidermal growth factor receptor activation by transforming growth factor alpha ( TGF alpha ) has been implicated in growth stimulation during epithelial neoplasia
Tekpetey et al., J Assist Reprod Genet 1995 : Epidermal growth factor (EGF) receptor localization in cultured human granulosa lutein cells and the stimulation of progesterone production by EGF and transforming growth factor-alpha ( TGF-alpha )
Lipeski et al., Biochem Mol Biol Int 1996 : A comparison of epidermal growth factor receptor mediated mitogenic signaling in response to transforming growth factor alpha and epidermal growth factor in cultured fetal rat hepatocytes
Shibata et al., Mol Carcinog 1997 (Carcinoma, Squamous Cell...) : Enhanced sensitivity to tumor growth and development in multistage skin carcinogenesis by transforming growth factor-alpha induced epidermal growth factor receptor activation but not p53 inactivation