Disease relevance of Egf

• In Rat 1 fibroblasts, stimulation of mitogen-activated protein (MAP) kinase via the IGF1 receptor and the Gi-coupled receptor for lysophosphatidic acid (LPA), but not via the EGF receptor, is sensitive both to pertussis toxin treatment and to cellular expression of a specific G beta gamma subunit-binding peptide [1].
• These findings suggest that the neurotrophic activity of EGF is maintained by afferent signals of midbrain dopaminergic neurons and is impaired in patients with Parkinson's disease [2].
• A rat pheochromocytoma cell line (PC12), when transfected with beta1,4-N-acetylglucosaminyltransferase III (GnT-III), which catalyzes the formation of a bisecting GlcNAc structure in N-glycans, resulted in the suppression of neurite outgrowth induced by costimulation of epidermal growth factor (EGF) and integrins [3].
• CONCLUSIONS: Because most breast carcinomas overexpress c-Src, it behooves one to question the extent to which reducing the amount of EGF and consequent EGFR activity will decrease invasion [4].
• Instead, our results indicate that in BT474 breast carcinoma cells, EGF can substitute for c-Src in promoting breast cancer cell invasion [4].

Psychiatry related information on Egf

• This study assessed if oxidative stress induced by treatment of PC12 cells with H2O2 modulated signaling cascades induced by nerve growth factor (NGF) or epidermal growth factor (EGF) because oxidative stress and impaired growth factor function are associated with aging and aging-associated diseases such as Alzheimer's disease [5].
• Such increase in ECM protein expression as well as astrocyte permissiveness to neurite outgrowth was reversed by the specific EGF receptor tyrosine kinase inhibitor, tyrphostin [6].
• At the adult stage, EGF-treated rats were challenged with cocaine (15 mg/kg) or methamphetamine (1 mg/kg), and conditioned place preference and locomotor activity were examined [7].
• This EtOH-related alteration of the gastric EGF receptor may be one of the mechanisms underlying the gastric pathology associated with alcohol abuse [8].
• Epidermal growth factor induced cytosolic free calcium oscillations consisting of periodic trains of spikes with a latency period of up to several minutes [9].

High impact information on Egf

• Reconstitution of unresponsive membranes with purified C kinase alters phosphorylation of the EGF receptor and restores the inhibitory effect of phorbol esters on 125I-EGF binding previously observed only in intact cells [10].
• Preventing calcium entry with EGTA or enhancing intracellular calcium with A23187 in intact cells modulates EGF receptor affinity in membranes isolated subsequently [10].
• Also, EGTA attenuates the usual inhibition of EGF binding caused by phorbol esters [10].
• NRK fibroblasts exposed to transforming growth factor-beta (TGF-beta) show increased binding of radiolabeled epidermal growth factor (EGF) relative to untreated cells [11].
• Transforming growth factor-beta controls receptor levels for epidermal growth factor in NRK fibroblasts [11].

Chemical compound and disease context of Egf

• Activation of p42/p44 mitogen-activated protein kinase by angiotensin II, vasopressin, norepinephrine, and prostaglandin F2alpha in hepatocytes is sustained, and like the effect of epidermal growth factor, mediated through pertussis toxin-sensitive mechanisms [12].
• The artificial sweetener saccharin inhibits binding of epidermal growth factor (EGF) to cultured rat pituitary tumor cells (GH4C1 cells) [13].
• The present study was undertaken to examine the effect of long term exposure to epidermal growth factor (EGF) on thyroid hormone responses as well as the concentration of specific nuclear thyroid hormone receptors in GH4C1 rat pituitary tumor cells [14].
• In contrast RC-160 did inhibit the EGF-stimulated growth of a rat pancreatic cancer cell line AR42J [15].
• Long-term treatment of rat pituitary tumor cells with epidermal growth factor (EGF) inhibits 45Ca2+ uptake, intracellular calcium levels and subsequent prolactin secretion in response to membrane depolarization [16].

Biological context of Egf

• Since EGF is produced in kidney, our findings are consistent with intrarenal paracrine regulation of IGF I gene expression by EGF [17].
• Epidermal growth factor induces phosphorylation of extracellular signal-regulated kinase 2 via multiple pathways [18].
• Down-regulation of EGFR expression through pretreatment of cells with EGF also attenuated ERK activation and Shc tyrosine phosphorylation in response to arsenite treatment [19].
• The transformed phenotype induced by EGF in the EGFR cells was dependent upon both Ras and RalA [20].
• However, suppression of TGF-beta(1)-induced apoptosis by EGF and TNF-alpha occurs via different protein kinase signaling pathways [21].

Anatomical context of Egf

• BACKGROUND & AIMS: Previous studies have shown that gastric ulceration stimulates epithelial cell proliferation and overexpression of epidermal growth factor (EGF) and EGF receptor (EGF-R) in the mucosa bordering necrosis [22].
• Here we report that expression of p21rasAsn-17 does not abolish epidermal growth factor (EGF)-induced phosphorylation of ERK2 in fibroblasts [18].
• Epidermal growth factor-induced activation of the insulin-like growth factor I receptor in rat hepatocytes [23].
• We found that Ras was transiently stimulated upon both EGF and NGF treatment of PC12 cells [24].
• 125I-EGF binding was not altered if cells were incubated at 4 degrees C, although TRH receptors were saturated or in a variant pituitary cell line without TRH receptors [25].

Associations of Egf with chemical compounds

• We also examined the effect of Tyrphostin A46 (potent inhibitor of EGF-R and EGF-R kinase-dependent proliferation) on the above parameters [22].
• Arsenite treatment rapidly stimulated tyrosine phosphorylation of several proteins in a Ras-independent manner, with a pattern similar to that seen in response to epidermal growth factor (EGF) treatment [19].
• In rat-1 cells, inhibition of either PKC, by prolonged 12-O-tetradecanoylphorbol-13-acetate (TPA) pretreatment, or calcium influx, by ethylene glycol-bis(beta-aminoethyl ether)-N,N,N',N'-tetraacetic acid (EGTA) pretreatment, did not abolish EGF-induced ERK2 phosphorylation [18].
• 5-HT2A receptor induces ERK phosphorylation and proliferation through ADAM-17 tumor necrosis factor-alpha-converting enzyme (TACE) activation and heparin-bound epidermal growth factor-like growth factor (HB-EGF) shedding in mesangial cells [26].
• The endogenous Gene 33 polypeptide is induced by EGF, platelet-derived growth factor, serum, and dexamethasone (Dex) in Rat 2 rat fibroblasts [27].

Physical interactions of Egf

• Effect of epidermal growth factor on placental amino acid transport and regulation of epidermal growth factor receptor expression of hepatocyte in rat [28].
• Here we investigated the role of nuclear and cytosolic Ca(2+) signals in epidermal growth factor (EGF)-induced transactivation of the ternary complex factor Elk-1 using a GAL4-Elk-1 construct [29].
• In an in vitro assay, TAS-301 inhibited the migration of smooth muscle cells (SMCs) stimulated by platelet-derived growth factor-BB, insulin-like growth factor-1 or heparin-binding epidermal growth factor-like growth factor [30].
• Scatchard analyses revealed that EGF receptors bound EGF with 4- to 8-fold higher affinity than TGF-alpha [31].
• Angiotensin AT(1) and AT(2) receptors differentially regulate angiopoietin-2 and vascular endothelial growth factor expression and angiogenesis by modulating heparin binding-epidermal growth factor (EGF)-mediated EGF receptor transactivation [32].

Enzymatic interactions of Egf

• Both TRH and EGF induced the association of tyrosine phosphorylated Shc proteins with a fusion protein containing SH2 and SH3 domains of Grb2, another important component in ras activation [33].
• Soluble extracts from serum- or epidermal growth factor-stimulated Swiss 3T3 cells show up to a 25-fold increase in their ability to phosphorylate 40 S ribosomal protein S6 [34].
• In preliminary studies, monensin (10 microM) produced a 32%-50% shift of Tf-R from the surface to the inside, whereas short-term incubation with epidermal growth factor (0.17 mM) brought about no clear-cut Tf-R redistribution [35].
• Transformation by pp60src or stimulation of cells with epidermal growth factor induces the stable association of tyrosine-phosphorylated cellular proteins with GTPase-activating protein [36].
• In the present report, we have demonstrated in a cell-free system that solubilized epidermal growth factor receptors can phosphorylate tyrosine residues in pp120 [37].

Regulatory relationships of Egf

• Insulin-like growth factor I gene expression in isolated rat renal collecting duct is stimulated by epidermal growth factor [17].
• In contrast, stimulation with epidermal growth factor induces a transient activation of p42 and p44 MAP kinases without pronounced nuclear translocation and does not trigger cell differentiation [38].
• Immunoprecipitation of Shc from EGF-stimulated cells removed almost all EGFR-associated Grb2 [39].
• In contrast, ERK2 was highly activated by EGF treatment, but the magnitude of activation was significantly lower in hepatocytes of aged animals compared to those of young animals (7-fold versus 20-fold, respectively) [40].
• Neither stable nor transient overexpression of nPKCepsilon produced enhancement of EGF- or TRH-induced PRL promoter activity, suggesting that different processes regulate PRL transcription and hormone secretion [41].

Other interactions of Egf

• The antiapoptotic capacity of the IGF-I receptor was not shared by other growth factors tested, including epidermal growth factor (EGF) and thrombin, although the cells expressed functional receptors for all the agonists [42].
• Under these conditions, prolactin mRNA was only slightly (4-fold) increased by EGF [43].
• Furthermore, immunodepletion of Shc proteins from membrane fractions of EGF-stimulated cells removed 93% of the ras GEF activity, whereas, precipitation of EGFR had only a small effect on ras GEF activity [39].
• Age-related decline in mitogen-activated protein kinase activity in epidermal growth factor-stimulated rat hepatocytes [40].
• No significant effects were observed with TGF-alpha, EGF, or HGF [44].

Analytical, diagnostic and therapeutic context of Egf

• Tyrosine 1173 of the EGF receptor is underphosphorylated in the hepatocytes from old animals compared with young in a Western blot analysis using a phosphospecific antibody that recognizes phosphotyrosine 1173 of the EGF receptor [45].
• Human pancreatic tumor cells (PANC-1) and normal rat kidney cells (NRK), as a control, were treated with 30 ng/ml EGF for 0, 5, and 20 min before fixation and viewing by electron microscopy [46].
• The enhanced green fluorescent protein-tagged pleckstrin homology (PH) domain of protein kinase B, which selectively binds to phosphatidylinositol 3,4-bisphosphate and phosphatidylinositol 3,4,5-triphosphate, was translocated to the plasma membrane after treatment with either EGF or NGF [47].
• Signal transducer and activator of transcription (STAT) proteins may be activated by epidermal growth factor (EGF), but their role in EGF receptor-mediated mitogenic signaling is not clear [48].
• In astroglial cells cultured in serum-free medium, IGF1, PDGF, and EGF, which stimulate cell proliferation, increased PI(3)-kinase activity immunoprecipitated with anti-phosphotyrosine antibodies as shown by thin layer chromatography and high performance liquid chromatography [49].

References