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 common PDGF receptor is activated by homodimeric A and B forms of PDGF

The human platelet-derived growth factor (PDGF) receptor complementary DNA was cloned and expressed by transfection of Chinese hamster ovary (CHO) fibroblasts. The ability of CHO cells expressing the human receptor complementary DNA (CHO-HR5) to interact with different recombinant forms of PDGF (AA and BB homodimers) was tested. Both forms of PDGF bind to the transfected receptor, stimulate the receptor tyrosine kinase activity, and elicit a mitogenic response in a manner that was indistinguishable from the responses of Balb/c 3T3 cells to AA and BB forms of PDGF can be attributed to a single type of receptor and show that the AA form, like the BB form, is a true mitogen.     

Autocrine stimulation of intracellular PDGF receptors in v-sis-transformed cells

Autocrine activation of platelet-derived growth factor (PDGF) receptors is the mechanism of transformation by the v-sis oncogene. Since the addition of PDGF does not transform normal cells, autocrine mechanisms may involve unique pathways of receptor activation. In this study autocrine stimulation of the PDGF receptor was observed in v-sis-transformed normal rat kidney (NRK) cells. In contrast to receptor activation in normal cells, autocrine activation of PDGF receptors in v-sis-transformed cells occurred in intracellular compartments, disrupting receptor processing and diverting receptors and their precursors to a chloroquine-sensitive degradation pathway. These findings show that intracellular activation of receptors by autocrine mechanisms may play a role in cell transformation.     

从EUREPGAP-TEA到中国茶叶良好农业规范

中国种茶历史悠久,茶叶种类丰富,茶文化源远流长,茶产业更是成为不少地区农民增收的支柱产业。而中国出口茶叶却要接受西方标准,常导致出口受阻,甚至遭遇退货,对中国茶叶国际竞争力提高极为不利。为此,急需引进吸收国际通行的良好农业规范(GAP),提升中国茶产业。本文介绍了GAP的背景知识、欧盟茶叶GAP标准和中国茶叶GAP标准的比对情况,提出了发展建议。     

Two classes of PDGF receptor recognize different isoforms of PDGF

Previous studies involving platelet-derived growth factor (PDGF) have been based on the premise that a single cell-surface receptor binds all three isoforms of PDGF (AA, BB, and AB). It is now shown that two populations of PDGF receptor exist and can be distinguished by their ligand binding specificity. The B receptor binds only the BB dimer, whereas the A/B receptor binds AA, BB, and AB dimers. Human dermal fibroblasts appear to express seven times as much B receptor as A/B receptor. The B receptor is responsible for most PDGF receptor phosphorylation.     

Molecular localization of the transforming and secretory properties of PDGF A and PDGF B

Human platelet-derived growth factor (PDGF) is a connective tissue cell mitogen comprised of two related chains encoded by distinct genes. The B chain is the homolog of the v-sis oncogene product. Properties that distinguish these ligands include greater transforming potency of the B chain and more efficient secretion of the A chain. By a strategy involving the generation of PDGF A and B chimeras, these properties were mapped to distinct domains of the respective molecules. Increased transforming efficiency segregated with the ability to activate both alpha and beta PDGF receptors. These findings genetically map PDGF B residues 105 to 144 as responsible for conformational alterations critical to beta PDGF receptor interaction and provide a mechanistic basis for the greater transforming potency of the PDGF B chain.     

良好农业规范(GAP)及其对中国农业的启示

GAP即良好农业规范,主要针对出售给消费者和加工企业的大多数农产品的种植、采收、清洗、摆放、包装和运输过程中常见微生物的危害控制以提高农产品的安全.20世纪90年代以后,国内外食品安全事故频发,人们对食品质量安伞日益重视;由此GAP应运而生.我国GAP事业起步较晚,为更好地进行农产品管理以及突破农产品对外贸易的"绿色壁垒",我国应不断发展CHINAGAP(中国GAP),早日完成国际接轨.     

Binding of DDT to lecithin

An interaction between DDT and lecithin is indicated by the reciprocal effects of each compound on the proton magnetic resonance spectrum of the other. The phosphoryl choline moiety of the lecithin and the benzylic proton of the DDT seem to be involved. The most pronounced response in the proton magnetic resonance spectrum of the lecithin produced by increasing concentration s of DDT was a change in the chemical shift of the resonance peak due to the protons of the choline methyl groups. Increasing concentrations of lecithin produced changes in the chemical shift of the resonance peaks of the benzylic proton and adjacent ring protons of the DDT. Equilibrium constant of 0.597 +/-0.015 molal(-1) was obtained for this interaction.     

Diminished response of Werner's syndrome fibroblasts to growth factors PDGF and FGF

Patients with Werner's syndrome, an autosomal recessive disorder, undergo an accelerated aging process that leads to premature death. Fibroblasts from such patients typically grow poorly in culture. Here it is shown that fibroblasts from a patient with Werner's syndrome have a markedly attenuated mitogenic response to platelet-derived growth factor (PDGF) and fibroblast growth factor (FGF). In contrast, they have a full mitogenic response to fetal bovine serum. Both PDGF binding and receptor numbers per cell are unaltered. The Werner's syndrome cells express high constitutive levels of collagenase in vitro. Although PDGF enhances collagenase expression through increased levels of hybridizable collagenase messenger RNA in normal skin fibroblasts, no induction of collagenase occurs in the Werner's syndrome fibroblasts. Moreover, the failure to respond to this agonist effect of PDGF is not restored by fetal bovine serum. The data suggest that failure of one or more PDGF-mediated pathways in Werner's syndrome cells may contribute to the phenotypic expression of the disorder.     

Vascular permeability factor, an endothelial cell mitogen related to PDGF

Vascular permeability factor (VPF) is a 40-kilodalton disulfide-linked dimeric glycoprotein that is active in increasing blood vessel permeability, endothelial cell growth, and angiogenesis. These properties suggest that the expression of VPF by tumor cells could contribute to the increased neovascularization and vessel permeability that are associated with tumor vasculature. The cDNA sequence of VPF from human U937 cells was shown to code for a 189-amino acid polypeptide that is similar in structure to the B chain of platelet-derived growth factor (PDGF-B) and other PDGF-B-related proteins. The overall identity with PDGF-B is 18%. However, all eight of the cysteines in PDGF-B were found to be conserved in human VPF, an indication that the folding of the two proteins is probably similar. Clusters of basic amino acids in the COOH-terminal halves of human VPF and PDGF-B are also prevalent. Thus, VPF appears to be related to the PDGF/v-sis family of proteins.     

Mitogenesis in response to PDGF and bombesin abolished by microinjection of antibody to PIP2

The turnover of phosphatidylinositol 4,5-bisphosphate (PIP2) is believed to constitute a crucial step in the signaling pathways for stimulation of cells by a variety of bioactive substances, including mitogens, but decisive evidence for the idea has not been obtained. In the present study, a monoclonal antibody to PIP2 was microinjected into the cytoplasm of NIH 3T3 cells before or after exposure to mitogens. The antibody completely abolished nuclear labeling with [3H]thymidine induced by platelet-derived growth factor and bombesin, but not by fibroblast growth factor, epidermal growth factor, insulin, or serum. The findings strongly suggest that PIP2 breakdown is crucial in the elicitation and sustaining of cell proliferation induced by some types of mitogens such as platelet-derived growth factor and bombesin.     

我国GAP分析的研究进展

综述了GAP分析提出的原因及其涵义,总结了具有代表性的GAP分析的基本步骤和简单流程,归纳了我国GAP分析的研究区域、研究对象和研究尺度,介绍了我国GAP分析的研究方法,并针对国外GAP分析的研究进展,提出我国GAP分析的研究现状中目前存在的问题及未来发展的趋势。     

如何创建湖北省中药材GAP网站

针对湖北省当前中药材GAP的发展现状,分析了创建中药材GAP网站的必要性和可行性;阐述了创建网站所需要具备的条件以及方法,并对网站的推广提出了建议;为中药材生产的信息化提供参考.     

胆木GAP种植的环境评价

对海南省胆木(Nauclea officinalis)主要生产区环境包括土壤、地表水及大气进行采样综合分析评价。结果表明,胆木GAP种植基地海南省琼中县新市农场规划区大气环境、水资源、土壤环境均达到GAP标准,说明胆木GAP种植区环境质量良好,符合药材种植的环境质量要求。本研究为制定胆木生产技术规范和建立胆木GAP种植基地提供了科学依据。     

GAP基础与EUREPGAP应用研究

随着食品经济的迅速变化和全球化发展,农产品质量安全引起了广大利益相关者对农产品生产、农产品安全以及农业环境可持续性的空前关注。良好农业操作规范(GAP)作为一种农产品质量安全生产和管理工具,在各国得到了快速的推广与实施,但中国对于GAP的认识还很薄弱,系统地对GAP进行     

Role of phosphatidylinositol kinase in PDGF receptor signal transduction

The molecules with which the platelet-derived growth factor (PDGF) receptor interacts to elicit the biochemical reactions responsible for cell proliferation have not been identified. Antisera directed against specific PDGF receptor peptides coprecipitated a phosphatidylinositol (PI) kinase and the PDGF receptor. Immunoprecipitates from PDGF-stimulated cells contained 10 to 50 times as much PI kinase as those from unstimulated cells. Mutation of the PDGF receptor by deletion of its kinase insert region resulted in a receptor markedly less effective than the wild type in eliciting cell proliferation and defective in PDGF-stimulated PI kinase, but still capable of PDGF-induced receptor autophosphorylation and phosphoinositide hydrolysis. These data show that the PDGF receptor is physically associated with a PDGF-sensitive PI kinase that is distinct from tyrosine kinase and is not required for PDGF-induced PI hydrolysis. The finding that the mutant PDGF receptor missing the kinase insert domain elicited known early biochemical responses to PDGF, but did not associate with or regulate PI kinase, suggests a novel role for the receptor-associated PI kinase in the transmission of mitogenic signals.     

烟草GAP管理体系的建立与应用

根据CORESTA GAP指南,结合文山州烟叶生产条件与自然生态特点,建立了烟草GAP管理体系,并开展了应用。通过GAP管理体系的应用,取得积极效果:化学农药的使用得到有效控制,烟田使用农药有效成分总量为1.87 kg/hm2,示范区烟叶中农药残留种类及含量降低,符合CORESTA农药残留限量标准,烟叶安全性提高。烟叶中非烟物质得到较好控制,尤其是一类非烟物质得到有效控制,提高了客户的满意度。     

以农业良好操作规程(GAP)应对日本肯定列表制度

日本食品残留农业化学品肯定列表制度（以下简称肯定列表制度）是迄今为止世界上最庞大的食品、农产品、兽药残留标准体系，已于2006年5月29日正式实施。浙江省众多农产品、食品出口企业应怎样面对，反应不一，归纳起来大致有四种情况：第一种类型是积极主动型，他们得到的相关信息比较早，[第一段]     

对宁夏回族自治区推行中药材GAP的几点建议

针对宁夏回族自治区中药材生产的现状,就宁夏地区推行中药材GAP生产提出了加强野生药材资源保护、加强中药材品种选优和新品种培育、开展栽培品种提纯复状研究、研究中药材设施栽培技术、制定道地药材的质量标准等建议,并提出制订SOP操作规程的几点注意事项。     

CYK-4/GAP provides a localized cue to initiate anteroposterior polarity upon fertilization

The Caenorhabditis elegans anteroposterior axis is established in response to fertilization by sperm. Here we present evidence that RhoA, the guanine nucleotide-exchange factor ECT-2, and the Rho guanosine triphosphatase-activating protein CYK-4 modulate myosin light-chain activity to create a gradient of actomyosin, which establishes the anterior domain. CYK-4 is enriched within sperm, and paternally donated CYK-4 is required for polarity. These data suggest that CYK-4 provides a molecular link between fertilization and polarity establishment in the one-cell embryo. Orthologs of CYK-4 are expressed in sperm of other species, which suggests that this cue may be evolutionarily conserved.