scholarly journals EGF receptor ligands: recent advances

F1000Research ◽  
2016 ◽  
Vol 5 ◽  
pp. 2270 ◽  
Author(s):  
Bhuminder Singh ◽  
Graham Carpenter ◽  
Robert J. Coffey
Keyword(s):  
Growth Factor ◽  
Egf Receptor ◽  
Transforming Growth Factor ◽  
Heparin Binding ◽  
Receptor Ligands ◽  
Affinity Ligands ◽  
Egfr Ligands ◽  
Ligand Interactions ◽  
Epidermal Growth ◽  
The Individual

Seven ligands bind to and activate the mammalian epidermal growth factor (EGF) receptor (EGFR/ERBB1/HER1): EGF, transforming growth factor-alpha (TGFA), heparin-binding EGF-like growth factor (HBEGF), betacellulin (BTC), amphiregulin (AREG), epiregulin (EREG), and epigen (EPGN). Of these, EGF, TGFA, HBEGF, and BTC are thought to be high-affinity ligands, whereas AREG, EREG, and EPGN constitute low-affinity ligands. This focused review is meant to highlight recent studies related to actions of the individual EGFR ligands, the interesting biology that has been uncovered, and relevant advances related to ligand interactions with the EGFR.

115 RAT EPIDERMAL GROWTH FACTOR GENE EXPRESSION CONTROLLED BY PROGESTERONE DURING PREGNANCY

2008 ◽  
Vol 20 (1) ◽  
pp. 138
Author(s):  
H.-S. Byun ◽  
S.-H. Ko ◽  
G.-S. Lee ◽  
S.-H. Hyun ◽  
E.-B. Jeung
Keyword(s):  
Growth Factor ◽  
Epidermal Growth Factor ◽  
Egf Receptor ◽  
Transforming Growth Factor ◽  
Expression Patterns ◽  
Uterine Wall ◽  
Mrna Levels ◽  
Heparin Binding ◽  
Pregnant Rats ◽  
Epidermal Growth

The implantation of the developing blastocyst into the uterine wall is regulated by a precisely timed interplay of the ovarian hormones estrogen and progesterone, which control a set of regulatory factors that make the uterus receptive to implantation. These factors include EGF receptor (Egfr) and members of the epidermal growth factor (Egf) family, namely, EGF, heparin-binding EGF (Hbegf), transforming growth factor-alpha (Tgfa), and amphiregulin (Areg). However, the exact role(s) these factors play in pregnancy remain unclear. To address this, a group of three rats was euthanized every day from gestation day (GD) 0 through to GD21. The uterus, attached uterus (these tissues are mostly composed of stromal cells), and placenta were rapidly excised and used directly for total RNA. We used real-time PCR with the TaqMan system (Applied Biosystems, Foster City, CA, ISA) to examine the uterine expression patterns of these factors in rats during the entire pregnancy. Data were analyzed by nonparametric one-way analysis of variance using the Kruskal-Wallis test, followed by Dunnett's test for multiple comparisons. Egf and Egfr mRNA levels increased significantly at implantation, especially on GD3 and GD6, after which their expression gradually decreased. Hbegf and Tgfa showed a modest spike of transcription around the implantation period (GD4 and GD3, respectively) but were much more strongly expressed at mid-pregnancy, which is when progesterone is secreted at high levels. Areg expression peaked strongly around implantation (GD4) and at mid-pregnancy (GD12). Treatment of pregnant rats on GD5 or GD8 with the progesterone receptor antagonist RU486 (2.5 mg per rat) blocked the expression of all of the genes on the days of treatment. Moreover, injection of immature rats with progesterone induced the uterine expression of all of the genes except Hbegf, while injection with estrogen or estrogen plus progesterone had no effect. Taken together, all genes tested may be assumed to regulate the implantation process. Moreover, Hbegf, Tgfa, and Areg may participate during mid-pregnancy. In addition, all of these activities are likely to be controlled by progesterone in the uterus of rats during pregnancy.

scholarly journals Redundant roles of EGFR ligands in the ERK activation waves during collective cell migration

2021 ◽  
Vol 5 (1) ◽  
pp. e202101206
Author(s):  
Shuhao Lin ◽  
Daiki Hirayama ◽  
Gembu Maryu ◽  
Kimiya Matsuda ◽  
Naoya Hino ◽  
...  
Keyword(s):  
Cell Migration ◽  
Growth Factor ◽  
Epidermal Growth Factor ◽  
Transforming Growth Factor ◽  
Collective Cell Migration ◽  
Heparin Binding ◽  
Erk Activation ◽  
Egfr Ligands ◽  
Egfr Ligand ◽  
Epidermal Growth

Epidermal growth factor receptor (EGFR) plays a pivotal role in collective cell migration by mediating cell-to-cell propagation of extracellular signal-regulated kinase (ERK) activation. Here, we aimed to determine which EGFR ligands mediate the ERK activation waves. We found that epidermal growth factor (EGF)–deficient cells exhibited lower basal ERK activity than the cells deficient in heparin-binding EGF (HBEGF), transforming growth factor alpha (TGFα) or epiregulin (EREG), but all cell lines deficient in a single EGFR ligand retained the ERK activation waves. Surprisingly, ERK activation waves were markedly suppressed, albeit incompletely, only when all four EGFR ligands were knocked out. Re-expression of the EGFR ligands revealed that all but HBEGF could restore the ERK activation waves. Aiming at complete elimination of the ERK activation waves, we further attempted to knockout NRG1, a ligand for ErbB3 and ErbB4, and found that NRG1-deficiency induced growth arrest in the absence of all four EGFR ligand genes. Collectively, these results showed that EGFR ligands exhibit remarkable redundancy in the propagation of ERK activation waves during collective cell migration.

scholarly journals Ligand-independent Dimer Formation of Epidermal Growth Factor Receptor (EGFR) Is a Step Separable from Ligand-induced EGFR Signaling

2002 ◽  
Vol 13 (7) ◽  
pp. 2547-2557 ◽  
Author(s):  
Xiaochun Yu ◽  
Kailash D. Sharma ◽  
Tsuyoshi Takahashi ◽  
Ryo Iwamoto ◽  
Eisuke Mekada
Keyword(s):  
Growth Factor ◽  
Epidermal Growth Factor ◽  
Egf Receptor ◽  
Cytoplasmic Domain ◽  
Erythropoietin Receptor ◽  
Mutant Form ◽  
Chimeric Receptor ◽  
Heparin Binding ◽  
Egfr Ligands ◽  
Epidermal Growth

Dimerization and phosphorylation of the epidermal growth factor (EGF) receptor (EGFR) are the initial and essential events of EGF-induced signal transduction. However, the mechanism by which EGFR ligands induce dimerization and phosphorylation is not fully understood. Here, we demonstrate that EGFRs can form dimers on the cell surface independent of ligand binding. However, a chimeric receptor, comprising the extracellular and transmembrane domains of EGFR and the cytoplasmic domain of the erythropoietin receptor (EpoR), did not form a dimer in the absence of ligands, suggesting that the cytoplasmic domain of EGFR is important for predimer formation. Analysis of deletion mutants of EGFR showed that the region between835Ala and918Asp of the EGFR cytoplasmic domain is required for EGFR predimer formation. In contrast to wild-type EGFR ligands, a mutant form of heparin-binding EGF-like growth factor (HB2) did not induce dimerization of the EGFR-EpoR chimeric receptor and therefore failed to activate the chimeric receptor. However, when the dimerization was induced by a monoclonal antibody to EGFR, HB2 could activate the chimeric receptor. These results indicate that EGFR can form a ligand-independent inactive dimer and that receptor dimerization and activation are mechanistically distinct and separable events.

Met -/- kidneys express epithelial cells that chemotax and form tubules in response to EGF receptor ligands

1997 ◽  
Vol 272 (2) ◽  
pp. F222-F228
Author(s):  
C. Kjelsberg ◽  
H. Sakurai ◽  
K. Spokes ◽  
C. Birchmeier ◽  
I. Drummond ◽  
...  
Keyword(s):  
Growth Factor ◽  
Epithelial Cell ◽  
Egf Receptor ◽  
Transforming Growth Factor ◽  
Growth Factor Receptor ◽  
Receptor Ligands ◽  
Tubule Formation ◽  
Human Papillomavirus 16 ◽  
Immortalized Cells

The growth factor/receptor combination of hepatocyte growth factor (HGF)/c-met has been postulated to be critical for mesenchymal-to-epithelial conversion and tubule formation in the developing kidney. We therefore isolated and immortalized cells from embryonic kidneys of met -/- transgenic mice to determine whether these cells were epithelial and able to chemotax and form tubules in vitro. The cells were immortalized with retrovirus expressing human papillomavirus 16 (HPV 16) E6/E7 genes. Two rapidly dividing clones were isolated and found to express the epithelial cell markers cytokeratin, zonula occludens-1, and E-cadherin but not to express the fibroblast marker vimentin. The met -/- cells were able to chemotax in response to epidermal growth factor and transforming growth factor-alpha (TGF-alpha) and form tubules in vitro in response to TGF-alpha but not HGF. These experiments suggest that the HGF/c-met axis is not essential for epithelial cell development in the embryonic kidney and demonstrate that other growth factors are capable of supporting early tubulogenesis.

scholarly journals An insulin epidermal growth factor-binding protein from Drosophila has insulin-degrading activity.

1989 ◽  
Vol 108 (1) ◽  
pp. 177-182 ◽  
Author(s):  
J V Garcia ◽  
M P Stoppelli ◽  
S J Decker ◽  
M R Rosner
Keyword(s):  
Growth Factor ◽  
Egf Receptor ◽  
Transforming Growth Factor ◽  
Binding Protein ◽  
Polyclonal Antiserum ◽  
Insulin Degrading Enzyme ◽  
Developmentally Regulated ◽  
Degrading Enzyme ◽  
Epidermal Growth ◽  
Factor Alpha

We have recently described the purification and characterization of an insulin-degrading enzyme (IDE) from Drosophila melanogaster that can cleave porcine insulin, is highly conserved through evolution and is developmentally regulated. We now report that the IDE is, in fact, an insulin EGF-binding protein (dp100) that we had isolated previously from Drosophila using an antihuman EGF receptor antiserum. This conclusion is based upon the following evidence. (a) dp100, identified by its ability to cross-link to labeled insulin, EGF, and transforming growth factor-alpha (TGF-alpha), and to be immunoprecipitated by anti-EGF receptor antisera, copurifies with the IDE activity. Thus, the purified IDE can be affinity labeled with either 125I-insulin, 125I-EGF, or 125I-TGF-alpha, and this labeling is specifically inhibited with unlabeled insulin, EGF, and the insulin B chain. (b) The antiserum to the human EGF receptor, which recognizes dp100, is able to specifically immunoprecipitate the insulin-degrading activity. (c) The purified IDE preparation contains a single protein of 110 kD which is recognized by both the anti-EGF receptor antiserum and anti-Drosophila IDE antiserum. (d) Polyclonal antiserum to the purified IDE, which specifically recognized only the 110-kD band in Drosophila Kc cells, immunoprecipitates dp100 cross-linked to 125I-TGF-alpha and dp100 cross-linked to 125I-insulin from the purified IDE preparation. (e) EGF, which competes with insulin for binding to dp100, also inhibits the degradation of insulin by the purified IDE. These results raise the possibility that a functional interaction between the insulin and EGF growth factor families can occur which is mediated by the insulin-degrading enzyme.

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