Signal transduction through the EGF receptor transfected in IL-3-dependent hematopoietic cells

An expression vector for the epidermal growth factor (EGF) receptor was introduced into the 32D myeloid cell line, which is devoid of EGF receptors and absolutely dependent on interleukin-3 (IL-3) for its proliferation and survival. Expression of the EGF receptor conferred the ability to utilize EGF for transduction of a mitogenic signal. When the transfected cells were propagated in EGF, they exhibited a more mature myeloid phenotype than was observed under conditions of IL-3-directed growth. Moreover, exposure to EGF led to a rapid stimulation of phosphoinositide metabolism, while IL-3 had no detectable effect on phosphoinositide turnover either in control or EGF receptor-transfected 32D cells. Although the transfected cells exhibited high levels of functional EGF receptors, they remained nontumorigenic. In contrast, transfection of v-erbB, an amino-terminal truncated form of the EGF receptor with constitutive tyrosine kinase activity, not only abrogated the IL-3 growth factor requirement of 32D cells, but caused them to become tumorigenic in nude mice. These results show that a na?ve hematopoietic cell expresses all of the intracellular components of the EGF-signaling pathway necessary to evoke a mitogenic response and sustain continuous proliferation.     

六味地黄汤对发育迟缓胎鼠脑NGF、EGF表达影响

目的 观察补肾益髓经典方六味地黄汤对发育迟缓胎鼠脑神经生长因子（NGF）、表皮细胞生长因子（EGF）表达影响,并为宫细胞内脑发育迟缓的治疗提供支持。方法 10只孕鼠依照受孕先后顺序随机分成5组,正常组、模型组、六味地黄汤高剂量组、六味地黄汤中剂量组、六味地黄汤低剂量组,采用孕鼠被动吸烟复制胎鼠发育迟缓模型,正常组、模型组均灌胃蒸馏水,六味地黄汤高、中、低剂量组分别灌胃2.164、1.082、0.541 g/mL的六味地黄汤浓缩液。于孕19 d将5组孕鼠处死,称算每组活胎脑体质量比;采用免疫组化法检测胎鼠脑内NGF、EGF的表达。结果 被动吸烟可使胎鼠脑体质量比降低,六味地黄汤高剂量能增加脑体质量比;模型组NGF、EGF表达低于正常组（P<0.01）,治疗组NGF、EGF表达均高于模型组（P<0.01或P<0.05）。结论 孕期被动吸烟可以导致胎鼠脑发育迟缓,六味地黄汤能通过调控脑内NGF、EGF改善胎鼠脑的发育。     

Epidermal growth factor immunoreactive material in the central nervous system: location and development

Epidermal growth factor (EGF) is a potent mitogen with hormonal activity in the gastrointestinal tract. Material cross-reacting with EGF was detected in the central nervous system of the developing and adult albino rat by the indirect immunofluorescence technique. High concentrations of EGF-cross-reacting material were identified in forebrain and midbrain structures of pallidal areas of the brain. These include the globus pallidus, ventral pallidum, entopeduncular nucleus, substantia nigra pars reticulata, and the islands of Calleja . Thus, EGF may represent another gut-brain peptide with potential neurotransmitter-neuromodulator functions in pallidal structures of the extrapyramidal motor systems of the brain.     

Chimeric NGF-EGF receptors define domains responsible for neuronal differentiation

To determine the domains of the low-affinity nerve growth factor (NGF) receptor required for appropriate signal transduction, a series of hybrid receptors were constructed that consisted of the extracellular ligand-binding domain of the human epidermal growth factor (EGF) receptor (EGFR) fused to the transmembrane and cytoplasmic domains of the human low-affinity NGF receptor (NGFR). Transfection of these chimeric receptors into rat pheochromocytoma PC12 cells resulted in appropriate cell surface expression. Biological activity mediated by the EGF-NGF chimeric receptor was assayed by the induction of neurite outgrowth in response to EGF in stably transfected cells. Furthermore, the chimeric receptor mediated nuclear signaling, as evidenced by the specific induction of transin messenger RNA, an NGF-responsive gene. Neurite outgrowth was not observed with chimeric receptors that contained the transmembrane domain from the EGFR, suggesting that the membrane-spanning region and cytoplasmic domain of the low-affinity NGFR are necessary for signal transduction.     

EGF在哺乳动物卵母细胞体外受精中的作用

[目的]为卵母细胞的生长发育创造更加适宜的环境。[方法]对EGF的理化特性、作用机理及其在卵母细胞体外培养、体外受精和早期胚胎发育中的作用进行阐述。[结果]EGF、IGF和TGF等生长因子在哺乳动物卵母细胞体外培养中起很重要的作用,尤其是在无血清培养条件下。生长因子可大大提高卵母细胞的成熟率和受精率,并对受精卵的发育有很大的促进作用。在众多生长因子中研究的最多的就是EGF。EGF能够促进卵母细胞减数分裂、卵丘细胞扩散,调节卵母细胞胞质成熟。[结论]对EGF的深入研究对于提高哺乳动物卵子的体外成熟率、体外受精率以及胎儿的发育都具有重大意义,为体外受精等技术和胚胎工程的发展提高可靠的保障。但对清楚了解EGF及其受体的性质和作用机制仍存在很多问题,且对表皮生长因子对体外受精的作用研究较少。     

Mechanism of divergent growth factor effects in mesenchymal stem cell differentiation

Closely related signals often lead to very different cellular outcomes. We found that the differentiation of human mesenchymal stem cells into bone-forming cells is stimulated by epidermal growth factor (EGF) but not platelet-derived growth factor (PDGF). We used mass spectrometry-based proteomics to comprehensively compare proteins that were tyrosine phosphorylated in response to EGF and PDGF and their associated partners. More than 90% of these signaling proteins were used by both ligands, whereas the phosphatidylinositol 3-kinase (PI3K) pathway was exclusively activated by PDGF, implicating it as a possible control point. Indeed, chemical inhibition of PI3K in PDGF-stimulated cells removed the differential effect of the two growth factors, bestowing full differentiation effect onto PDGF. Thus, quantitative proteomics can directly compare entire signaling networks and discover critical differences capable of changing cell fate.     

表皮生长因子对动物肠道健康的影响

 表皮生长因子是一种重要的肽类物质,因具有特殊生理功能而逐渐成为当今研究的一道亮点。本文主要综述了EGF对动物肠道黏膜机械屏障、化学屏障和免疫屏障的影响,阐述了EGF对动物肠道分泌、消化和吸收功能的影响,从而探讨EGF对肠道健康的保护作用及其可能的作用机制,同时讨论了研究中存在的一些问题     

Modulation of epidermal growth factor receptors on 3T3 cells by platelet-derived growth factor

Platelet-derived growth factor does not compete with epidermal growth factor (EGF) for binding to EGF receptors on the murine 3T3 cell surface, but it modulates EGF receptors in two ways: (i) it induces a transient down regulation of EGF receptors and (ii) it inhibits EGF-induced down regulation of EGF receptors. These data suggest a common cellular internalization mechanism for the receptors for both hormones.     

Concentration Variations of Growth Factors in Colostrum and Normal Milk of Sows

An experiment was conducted to determine the concentration variation of epidermal growth factors (EGF), include insulin-like growth factor-Ⅰ(IGF-Ⅰ), transforming growth factor-beta(TGF-β), and basic fibroblast growth factor (bFGF) in colostrum and normal milk of sows within 35 days after parturition. The results showed that the concentration of EGF, IGF-Ⅰ, TGF-β, bFGF was significantly higher in colostrum than that in normal milk. The concentration of these growth factors in colostrum was significantly decreased with the stage lapse of lactation, and then they remained stable in normal milk. Parity had a slight effect on the concentration of these growth factors.     

Transforming growth factor-alpha: a more potent angiogenic mediator than epidermal growth factor

Transforming growth factor-alpha (TGF-alpha) and epidermal growth factor (EGF) are structurally related peptides. Purified human TGF-alpha produced in Escherichia coli and pure natural mouse EGF were compared for their ability to bind to target cells in vitro and to promote angiogenesis in the hamster cheek pouch bioassay. Both polypeptides were found to bind in vitro to several target cells, including endothelial cells, and to stimulate their DNA synthesis in an equipotent fashion. In vivo, however, TGF-alpha was more potent than EGF in promoting angiogenesis and, because TGF-alpha is known to be secreted by a variety of human tumors, it is suggested that this growth factor may contribute to tumor-induced angiogenesis.     

Mediation of wound-related Rous sarcoma virus tumorigenesis by TGF-beta

In Rous sarcoma virus (RSV)-infected chickens, wounding leads to tumor formation with nearly 100% frequency in tissues that would otherwise remain tumor-free. Identifying molecular mediators of this phenomenon should yield important clues to the mechanisms involved in RSV tumorigenesis. Immunohistochemical staining showed that TGF-beta is present locally shortly after wounding, but not unwounded controls. In addition, subcutaneous administration of recombinant transforming growth factor-beta 1 (TGF-beta 1) could substitute completely for wounding in tumor induction. A treatment protocol of four doses of 800 nanograms of TGF-beta resulted in v-src-expressing tumors with 100% frequency; four doses of only 10 nanograms still led to tumor formation in 80% of the animals. This effect was specific, as other growth factors with suggested roles in wound healing did not elicit the same response. Epidermal growth factor (EGF) or TGF-alpha had no effect, and platelet-derived growth factor (PDGF) or insulin-like growth factor-1 (IGF-1) yielded only occasional tumors after longer latency. TGF-beta release during the wound-healing response may thus be a critical event that creates a conducive environment for RSV tumorigenesis and may act as a cofactor for transformation in this system.     

短光照对绒山羊绒毛生长相关激素的影响

为研究控制光周期对绒山羊绒毛生长相关激素的影响,从短光照试验和对照组绒山羊中选择2周岁6对双胞胎绒山羊母羊,采集血液样品利用酶联免疫法进行激素含量测定,利用SAS9.0软件进行显著性检验和相关性分析。结果发现:一天24h当中,绒山羊进入棚圈后褪黑激素MLT(melatonin,mLT)和IGF-1含量显著增加,PRL含量显著减少,EGF和GH含量在2组中差异不显著;一年当中,进入光控棚圈后6月份绒山羊血液中的MLT(P0.05)、IGF-1和EGF(P0.05)含量均增加,PRL含量显著降低;9月份试验组绒山羊MLT、IGF-1和GH含量高于对照组(P0.05),PRL含量依然低于对照组(P0.05)。在相关性分析中,试验组和对照组PRL与其他激素之间的相关系数为负数;与对照组相比短光照明显增加了MLT与PRL、EGF,PRL与IGF-1、EGF、GH,IGF-1与EGF、GH,EGF与GH之间的相互作用(P0.05),减弱了MLT与IGF-1、GH之间的相互作用。结果表明,短光照通过增强各激素间的协同或拮抗作用而提前诱发绒毛生长。     

Binding of SH2 domains of phospholipase C gamma 1, GAP, and Src to activated growth factor receptors

Phospholipase C gamma 1 (PLC gamma 1) and p21ras guanosine triphosphatase (GTPase) activating protein (GAP) bind to and are phosphorylated by activated growth factor receptors. Both PLC gamma 1 and GAP contain two adjacent copies of the noncatalytic Src homology 2 (SH2) domain. The SH2 domains of PLC gamma 1 synthesized individually in bacteria formed high affinity complexes with the epidermal growth factor (EGF)- or platelet derived growth factor (PDGF)-receptors in cell lysates, and bound synergistically to activated receptors when expressed together as one bacterial protein. In vitro complex formation was dependent on prior growth factor stimulation and was competed by intracellular PLC gamma 1. Similar results were obtained for binding of GAP SH2 domains to the PDGF-receptor. The isolated SH2 domains of other signaling proteins, such as p60src and Crk, also bound activated PDGF-receptors in vitro. SH2 domains, therefore, provide a common mechanism by which enzymatically diverse regulatory proteins can physically associate with the same activated receptors and thereby couple growth factor stimulation to intracellular signal transduction pathways.     

A Study on the Inhibitory Potency of Protease Inhibitors in Porcine Colostrum

Porcine colostrum and milk were separated into the acid-soluble fraction (SF) and casein frac-tion (CF) by centrifuge. Trypsin and chymotrypsin inhibitory capacity in porcine colostrum, milk and theircomponents were determined by incubating bovine trypsin or chymotrypsin in a medium. The inhibition of in-sulin-like growth factor Ⅰ (IGF-Ⅰ) and epidermal growth factor (EGF) degradation in pig small intestinal con-tents by porcine colostrum was measured by incubating iodinated IGF-Ⅰ or EGF. Degradation of labeled IGF-Ⅰor EGF was determined by monitoring the generation of radioactivity soluble in 30% trichloroacetic acid(TCA). The results showed that porcine colostrum had high levels of trypsin and chymotrypsin inhibitory ac-tivity and increased the stability of IGF-Ⅰ and EGF in pig intestinal contents. The SF was higher in inhibitorypotency than CF. The present study revealed that the protease inhibitors in porcine colostrum, milk-derivedand colostrum-specific, existed mainly in SF.     

A heparin-binding growth factor secreted by macrophage-like cells that is related to EGF.

Macrophage-like U-937 cells secrete a 22-kilodalton heparin-binding growth factor that is mitogenic for BALB-3T3 fibroblasts and smooth muscle cells, but not endothelial cells. The amino acid sequence predicted from complementary DNA clones indicates that the mitogen is a new member of the epidermal growth factor (EGF) family. This heparin-binding EGF-like growth factor (HB-EGF) binds to EGF receptors on A-431 epidermoid carcinoma cells and smooth muscle cells, but is a far more potent mitogen for smooth muscle cells than is EGF. HB-EGF is also expressed in cultured human macrophages and may be involved in macrophage-mediated cellular proliferation.     

Epidermal-growth-factor-dependent transformation by a human EGF receptor proto-oncogene

The epidermal growth factor (EGF) receptor gene EGFR has been placed in a retrovirus vector to examine the growth properties of cells that experimentally overproduce a full-length EGF receptor. NIH 3T3 cells transfected with the viral DNA or infected with the corresponding rescued retrovirus developed a fully transformed phenotype in vitro that required both functional EGFR expression and the presence of EGF in the growth medium. Cells expressing 4 x 10(5) EGF receptors formed tumors in nude mice, while control cells did not. Therefore, the EGFR retrovirus, which had a titer on NIH 3T3 cells that was greater than 10(7) focus-forming units per milliliter, can efficiently transfer and express this gene, and increased numbers of EGF receptors can contribute to the transformed phenotype.     

Amphiregulin, a TH2 cytokine enhancing resistance to nematodes

Although type 2 immune responses contribute to allergy and asthma, these responses are essential for clearing intestinal helminth infestations by mechanisms that include increased epithelial shedding. We show that T helper 2 cells (T(H)2), but not other T cell subsets, express amphiregulin, a member of the epidermal growth factor (EGF) family. EGF receptor ligands directly induce epithelial cell proliferation, and lack of amphiregulin delayed expulsion of the nematode Trichuris muris. This newly recognized link between T(H)2 cells and epithelial proliferation should help in planning therapeutic interventions for helminth infections and other diseases that involve both cell proliferation and allergy, such as asthma.     

Expression of the beta-nerve growth factor gene in hippocampal neurons

In situ hybridization with complementary DNA probes for nerve growth factor (NGF) was used to identify cells containing NGF messenger RNA in rat and mouse brain. The most intense labeling occurred in hippocampus, where hybridizing neurons were found in the dentate gyrus and the pyramidal cell layer. The neuronal identity of NGF mRNA-containing cells was further assessed by a loss of NGF-hybridizing mRNA in hippocampal areas where neurons had been destroyed by kainic acid or colchicine. RNA blot analysis also revealed a considerable decrease in the level of NGF mRNA in rat dentate gyrus after a lesion was produced by colchicine. This lesion also caused a decrease in the level of Thy-1 mRNA and an increase in the level of glial fibrillary acidic protein mRNA. Neuronal death was thus associated with the disappearance of NGF mRNA. These results suggest a synthesis of NGF by neurons in the brain and imply that, in hippocampus, NGF influences NGF-sensitive neurons through neuron-to-neuron interactions.