Solution Structure of the Epidermal Growth Factor (EGF)-like Module of Human Complement Protease C1r, an Atypical Member of the EGF Family†

Biochemistry ◽  
1998 ◽  
Vol 37 (5) ◽  
pp. 1204-1214 ◽  
Author(s):  
Beate Bersch ◽  
Jean-François Hernandez ◽  
Dominique Marion ◽  
Gérard J. Arlaud
Keyword(s):  
Growth Factor ◽  
Epidermal Growth Factor ◽  
Solution Structure ◽  
Human Complement ◽  
Epidermal Growth ◽  
Egf Family ◽  
Atypical Member

166 DIFFERENTIAL EXPRESSION OF AMPHIREGULINE, EPIDERMAL GROWTH FACTOR, AND CALBINDIN-D9k IN THE UTERUS OF RODENTS AND PIGS DURING IMPLANTATION

2007 ◽  
Vol 19 (1) ◽  
pp. 200
Author(s):  
G.-S. Lee ◽  
M.-H. Kim ◽  
S.-H. Hyun ◽  
E.-B. Jeung
Keyword(s):  
Growth Factor ◽  
Epidermal Growth Factor ◽  
Calcium Binding ◽  
Mammalian Species ◽  
Apical Surface ◽  
Calbindin D9k ◽  
Complex Process ◽  
Epidermal Growth ◽  
Egf Family ◽  
Embryo Attachment

Implantation in mammalian species is a complex process that involves embryo apposition and attachment to the apical surface of the uterine epithelium. This process involves a variant of molecules that are not unique in themselves but play unique roles in the process of implantation. Among them, the epidermal growth factor (EGF) family, the cytokines, cell adhesion molecules, and calcium-binding proteins appear to be important in embryonic attachment. Amphireguline (Areg), its receptor (EGFR), and calbindin-D9k (CaBP-9k) were highly expressed before implantation. Thus, in the present study, using rodent and porcine models, the expression levels of Areg, EGFR, and CaBP-9k gene were analyzed in the uterus during the estrous cycle and pregnancy by means of RT-PCR to elucidate their roles in implantation. Areg and CaBP-9k were significantly up-regulated at diestrus; however, these transcripts disappeared at proestrus in mice. In addition, EGFR mRNA was primarily observed at diestrus in mice. Although CaBP-9k and EGFR transcripts of rats increased at proestrus, no Areg mRNA was observed in this model. To clarify the regulator of the mouse Areg gene, immature mice were injected with sex steroid hormones. No transcripts of Areg were detected in these models, suggesting that mouse Areg may require other puberty factors. Porcine expressions of uterine Areg, EGFR, and CaBP-9k mRNA fluctuated during pregnancy (Days 12, 15, 30, 60, 90, and 110 of pregnancy). CaBP-9k transcripts were highly expressed on Day 12 and decreased on Days 15 to 90. On Day 110, CaBP-9k mRNA was expressed as well. Areg mRNA increased on Days 12 to 30, and decreased on Days 30 to 110. EGFR transcripts were detected on Day 12 and gradually disappeared till the end of pregnancy. Uterine Areg and CaBP-9k mRNAs were regulated by progesterone (P4) in the mouse model. Areg transcripts of porcine uteri appear to be expressed after implantation, but CaBP-9k mRNA was induced before embryo attachment. Taken together, these results indicate taht uterine Areg, EGFR, and CaBP-9k are differentially regulated during pregnancy in these species, and porcine CaBP-9k could act as an important factor in implantation. A further spatial expression of these genes will contribute to the understanding of their complex molecular actions involved in embryo attachment.

scholarly journals Role of Epidermal Growth Factor Receptor Signaling in RAS-Driven Melanoma

2005 ◽  
Vol 25 (10) ◽  
pp. 4176-4188 ◽  
Author(s):  
Nabeel Bardeesy ◽  
Minjung Kim ◽  
Jin Xu ◽  
Ryung-Suk Kim ◽  
Qiong Shen ◽  
...  
Keyword(s):  
Growth Factor ◽  
Epidermal Growth Factor ◽  
Egf Receptor ◽  
Tumor Regression ◽  
Growth Factor Receptor ◽  
Tumor Model ◽  
Receptor Signaling ◽  
Epidermal Growth ◽  
Egf Family ◽  
Tumor Model System

ABSTRACT The identification of essential genetic elements in pathways governing the maintenance of fully established tumors is critical to the development of effective antioncologic agents. Previous studies revealed an essential role for H-RASV12G in melanoma maintenance in an inducible transgenic model. Here, we sought to define the molecular basis for RAS-dependent tumor maintenance through determination of the H-RASV12G-directed transcriptional program and subsequent functional validation of potential signaling surrogates. The extinction of H-RASV12G expression in established tumors was associated with alterations in the expression of proliferative, antiapoptotic, and angiogenic genes, a profile consistent with the observed phenotype of tumor cell proliferative arrest and death and endothelial cell apoptosis during tumor regression. In particular, these melanomas displayed a prominent RAS-dependent regulation of the epidermal growth factor (EGF) family, leading to establishment of an EGF receptor signaling loop. Genetic complementation and interference studies demonstrated that this signaling loop is essential to H-RASV12G-directed tumorigenesis. Thus, this inducible tumor model system permits the identification and validation of alternative points of therapeutic intervention without neutralization of the primary genetic lesion.

scholarly journals The Gene for Heparin-Binding Epidermal Growth Factor-Like Growth Factor is Stress-Inducible: Its Role in Cerebral Ischemia

1999 ◽  
Vol 19 (3) ◽  
pp. 307-320 ◽  
Author(s):  
Nobutaka Kawahara ◽  
Kazuhiko Mishima ◽  
Shigeki Higashiyama ◽  
Naoyuki Taniguchi ◽  
Akira Tamura ◽  
...  
Keyword(s):  
Cerebral Ischemia ◽  
Growth Factor ◽  
Epidermal Growth Factor ◽  
Dentate Gyrus ◽  
Transforming Growth Factor ◽  
Adult Brain ◽  
Normal Brain ◽  
Heparin Binding ◽  
Epidermal Growth ◽  
Egf Family

The functions of the epidermal growth factor (EGF) family members in the adult brain are not known. This study investigated the changes in the expression of members of the EGF family following global ischemia employing in situ hybridization and immunohistochemical techniques to elucidate their roles in pathological conditions. EGF mRNA was not detected in either the control or the postischemic rat brain. Although transforming growth factor-α (TGF-α) mRNA was widely expressed in the normal brain, its expression did not change appreciably following ischemia. By contrast, heparin-binding EGF-like growth factor (HB-EGF) mRNA expression was rapidly increased in the CA3 sector and the dentate gyrus of the hippocampus, cortex, thalamus, and cerebellar granule and Purkinje cell layers. EGF receptor mRNA, which was widely expressed, also showed an increase in the CA3 sector and dentate gyrus. Conversely, HB-EGF mRNA did not show any increase prior to ischemic neuronal injury in the CA1 sector, the region most vulnerable to ischemia. Immunohistochemical detection of HB-EGF in the postischemic brain suggested a slight increase of immunostaining in the dentate gyrus of the hippocampus and the cortex. These findings showed that the gene encoding HB-EGF is stress-inducible, indicating the like-lihood that HB-EGF is a neuroprotective factor in cerebral ischemia.

scholarly journals Role of membrane-anchored heparin-binding epidermal growth factor-like growth factor and CD9 on macrophages

1997 ◽  
Vol 328 (3) ◽  
pp. 923-928 ◽  
Author(s):  
Noriyuki OUCHI ◽  
Shinji KIHARA ◽  
Shizuya YAMASHITA ◽  
Shigeki HIGASHIYAMA ◽  
Tsutomu NAKAGAWA ◽  
...  
Keyword(s):  
Growth Factor ◽  
Epidermal Growth Factor ◽  
Surface Marker ◽  
Heparin Binding ◽  
Atherosclerotic Lesions ◽  
Growth Activity ◽  
Epidermal Growth ◽  
Egf Family ◽  
Formalin Fixed

Heparin-binding epidermal-growth-factor-like growth factor (HB-EGF) is a potent mitogen for smooth-muscle cells (SMCs) belonging to the EGF family. We have previously determined that HB-EGF is expressed in macrophages and SMCs of human atherosclerotic lesions and that its membrane-anchored precursor, proHB-EGF, also has a juxtacrine mitogenic activity which is markedly enhanced by CD9, a surface marker of lymphohaemopoietic cells. Therefore, when both proHB-EGF and CD9 are expressed on macrophages, they may strongly promote the development of atherosclerosis. In the present study we have investigated the changes in proHB-EGF and CD9 in THP-1 cells during differentiation into macrophages and by the addition of oxidized low-density lipoproteins (OxLDL) and assessed juxtacrine growth activity of THP-1 macrophages for human aortic SMCs. HB-EGF and CD9 at both the mRNA and the protein level were up-regulated after differentiation into macrophages, and further expression of HB-EGF was induced by the addition of OxLDL or lysophosphatidylcholine. Juxtacrine induction by formalin-fixed growth was suppressed to control levels by an inhibitor of HB-EGF and was partially decreased by anti-CD9 antibodies. These results suggest that co-expression of proHB-EGF and CD9 on macrophages plays an important role in the development of atherosclerosis by a juxtacrine mechanism.

174. THE EPIDERMAL GROWTH FACTOR (EGF) FAMILY IN THE ENDOMETRIUM AND BLASTOCYST OF THE TAMMAR WALLABY, MACROPUS EUGENII DURING EMBRYONIC DIAPAUSE

2009 ◽  
Vol 21 (9) ◽  
pp. 92
Author(s):  
J. C. Fenelon ◽  
G. Shaw ◽  
M. B. Renfree
Keyword(s):  
Growth Factors ◽  
Cell Division ◽  
Growth Factor ◽  
Epidermal Growth Factor ◽  
Tammar Wallaby ◽  
Leukaemia Inhibitory Factor ◽  
Embryonic Diapause ◽  
Macropus Eugenii ◽  
Epidermal Growth ◽  
Egf Family

Embryonic diapause, a suspension of cell division and growth at the blastocyst stage, is widespread amongst mammals, but is especially common in the kangaroos and wallabies. In the tammar, Macropus eugenii, the sequence of endocrine events leading to embryonic diapause and reactivation are well defined[1]. The blastocyst can remain in diapause for up to 11 months without cell division, measurable metabolism or apoptosis occurring [2]. The ovarian hormones, especially progesterone, exert their effects on the blastocyst by alterations in the endometrial secretions [3], but the molecular cross-talk between the endometrium and blastocyst is unknown. There is increasing evidence for the involvement of leukaemia inhibitory factor (LIF)but the epidermal growth factor (EGF) family of growth factors are also likely to be involved.This study examined the expression of EGF and HB-EGF as well as their receptors, ERBB1 and ERBB4, in the tammar endometrium and blastocyst at entry into, and reactivation from, diapause. The genes for these factors were highly conserved in the tammar with orthologues in human and mouse. Quantitative RT-PCR of all four factors in the endometrium showed that expression changed with stage. Although expression levels of both receptors did not change between diapause and reactivation, both HB-EGF and EGF levels increased at reactivation from diapause and levels of HB-EGF decreased at entry into diapause. All factors were immunopositive in the endometrium. Studies underway will determine whether the cellular location and quantity of these factors change with entry into or exit from diapause, and define the molecular interactions occurring between the blastocyst and endometrium. These results are consistent with a role for the EGF family of growth factors in the control of embryonic diapause in tammars.

scholarly journals Estrogen Negatively Regulates Epidermal Growth Factor (EGF)-Mediated Signal Transducer and Activator of Transcription 5 Signaling in Human EGF Family Receptor-Overexpressing Breast Cancer Cells

2005 ◽  
Vol 19 (11) ◽  
pp. 2660-2670 ◽  
Author(s):  
Julie L. Boerner ◽  
Matthew A. Gibson ◽  
Emily M. Fox ◽  
Erika D. Posner ◽  
Sarah J. Parsons ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Growth Factors ◽  
Growth Factor ◽  
Epidermal Growth Factor ◽  
Cancer Cells ◽  
Breast Cancer Cells ◽  
Egf Receptor ◽  
Signal Transducer ◽  
Epidermal Growth ◽  
Egf Family

Abstract Breast cancer cell growth may be stimulated by 17β-estradiol (E2) or growth factors like epidermal growth factor (EGF). However, tumors typically depend on only one of these pathways and may overexpress either estrogen receptor (ER) or EGF receptor (EGFR) and related family members. Tumors overexpressing EGFR are more aggressive than those expressing ER. Intracellular mediators of these growth-stimulatory pathways are not completely defined, but one potential common mediator of EGF and E2 signaling is the transcription factor signal transducer and activator of transcription 5 (STAT5). To investigate the role of STAT5 in potential crosstalk between E2 and EGF, MDA-MB231 and SKBr3 breast cancer cells, which are ER-negative and overexpress human EGF family receptors, were used. Introduction of ERα and treatment with E2 decreased EGF-induced tyrosine phosphorylation of STAT5b, basal and EGF-induced STAT5-mediated transcription, and EGF-stimulated DNA synthesis in these cells. Suppressive effects of E2-ΕRα were specific for STAT5, as EGF stimulation of MAPK was unaffected. Deletion/mutation analysis of ERα demonstrated that the DNA-binding domain was insufficient, and that the ligand-binding domain was required for these responses. ERα transcriptional activity was not necessary for suppression of STAT5 activity. Overexpression of c-Src did not prevent suppression of STAT5 activity by E2 and ERα. However, ERα did prevent basal increases in STAT5 activity with overexpressed c-Src. In the context of human EGF receptor family overexpression, E2-ER opposes EGF signaling by regulating STAT5 activity. STAT5 may be a crucial point of signaling for both E2 and growth factors in breast cancer cells, allowing targeted therapy for many types of breast tumors.

scholarly journals A high resolution 1 H NMR study of the solution structure of human epidermal growth factor

FEBS Letters ◽  
1986 ◽  
Vol 205 (1) ◽  
pp. 77-81 ◽  
Author(s):  
J.A. Carver ◽  
R.M. Cooke ◽  
G. Esposito ◽  
I.D. Campbell ◽  
H. Gregory ◽  
...  
Keyword(s):  
Growth Factor ◽  
High Resolution ◽  
Epidermal Growth Factor ◽  
Solution Structure ◽  
Human Epidermal Growth Factor ◽  
H Nmr ◽  
Nmr Study ◽  
Epidermal Growth

scholarly journals The N-terminal CUB-Epidermal Growth Factor Module Pair of Human Complement Protease C1r Binds Ca2+with High Affinity and Mediates Ca2+-dependent Interaction with C1s

1999 ◽  
Vol 274 (14) ◽  
pp. 9149-9159 ◽  
Author(s):  
Nicole M. Thielens ◽  
Karine Enrie ◽  
Monique Lacroix ◽  
Michel Jaquinod ◽  
Jean-François Hernandez ◽  
...  
Keyword(s):  
Growth Factor ◽  
Epidermal Growth Factor ◽  
Human Complement ◽  
High Affinity ◽  
Factor Module ◽  
Epidermal Growth ◽  
Dependent Interaction
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