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INHIBITORS OF GASTRIC-SECRETION - CURRENT PROGRESS

BRITISH JOURNAL OF SURGERY 1976年第10期63卷 788-792页

作者： CARTER, DC UNIV EDINBURGH DEPT CLIN SURGEDINBURGH EH10 5HFSCOTLAND

Several new compounds have become available recently which are potent inhibitors of gastric secretion. The therapeutic potential of these inhibitors in the peptic ulcer diathesis is reviewed and it is concluded that the histamine H2‐receptor antagonists show most promise at present. The prostaglandins and gastro‐intestinal polypeptides are of considerable physiological interest but are unlikely to have clinical importance in the immediate future.

关键词：表皮生长因子/药理学胃液/分泌胃黏膜/药物作用胃肠激素类/药理学胍类/药理学组胺H2拮抗剂/药理学咪唑类/药理学消化性溃疡/药物疗法前列腺素拮抗药/药理学前列腺素A类/药理学前列腺素E类/药理学分泌素/药理学生长抑素/药理学 Zollinger-Ellison综合征/药物疗法动物人类

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EGF-induced receptor autophosphorylation in primary hepatocytes isolated from phenobarbitone-treated mice

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BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS 1999年第2期260卷 483-487页

作者： Fletcher, K Lord, PG Orton, TC Chipman, JK Strain, AJ Queen Elizabeth Hosp Liver Res Labs Birmingham B15 2TH W Midlands England Univ Birmingham Sch Biochem Birmingham B15 2TT W Midlands England Zeneca Pharmaceut Dept Safety Med Macclesfield SK10 4TG Cheshire England

Phenobarbitone (PB) treatment of mice causes a decrease in the growth factor responsiveness of hepatocytes. Here, epidermal growth factor receptor (EGFR) expression and receptor autophosphorylation was determined in hepatocytes isolated from control and PB-treated mice. There was a decrease in the level of EGFR expression in hepatocytes isolated from mice following PB administration when compared to controls. EGF caused an approximate 20-fold increase of the 170 KD phosphotyrosine band in control hepatocytes, which was inhibited by the EGFR specific tyrosine kinase inhibitor 4,5-dianilinopthalamide. Following PB treatment, the degree of basal receptor phosphorylation (in the absence of EGF) was significantly greater and therefore the fold rise in EGFR phosphorylation in isolated hepatocytes was lower than in controls. However, the overall extent of EGF-induced receptor phosphorylation was not diminished in hepatocytes isolated from PH-treated mice. Therefore the reduction in responsiveness to growth factors seen in hepatocytes ex vivo or the cessation of proliferation observed in vivo following PH administration is unlikely to be attributed to a decrease in ligand binding and subsequent receptor autophosphorylation. (C) 1999 Academic Press.

关键词：印迹法蛋白质细胞培养的表皮生长因子/药理学肝/药物作用肝/代谢小鼠近交C57BL 苯巴比妥/药理学磷酰化受体表皮生长因子/代谢动物男(雄)性小鼠

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Usefulness of flow-cytometric cell sorting for enrichment of hepatic stem and progenitor cells in the liver

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TRANSPLANTATION PROCEEDINGS 2000年第2期32卷 249-251页

作者： Taniguchi, H Suzuki, A Zheng, Y Kondo, R Takada, Y Fukunaga, K Seino, K Yuzawa, K Otsuka, M Fukao, K Nakauchi, H Univ Tsukuba Inst Clin Med Dept Surg Tsukuba Ibaraki 3058575 Japan Univ Tsukuba Inst Basic Med Sci Dept Immunol Tsukuba Ibaraki 305 Japan Univ Tsukuba Japan Sci & Technol Corp Tsukuba Ibaraki 305 Japan

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INDUCTION BY SOLUBLE FACTORS OF ORGANIZED AXIAL STRUCTURES IN CHICK EPIBLASTS

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SCIENCE 1990年第4946期247卷 1092-1094页

作者： MITRANI, E SHIMONI, Y HEBREW UNIV JERUSALEM INST LIFE SCI DEPT ZOOL IL-91904 JERUSALEM ISRAEL

Inductive action of soluble factors was tested on isolated chick epiblasts. An assay was developed wherein conditioned medium derived from the Xenopus XTC cell line induced the formation of a full-length notochord and rows of bilaterally symetric somites. Basic fibroblast growth factor, epidermal growth factor, retinoic acid and transforming growth factor type .beta.1 and .beta.2 were not capable of inducing axial structures. Thus, soluble factors can elicit the development of polarity stored in the epiblast and behave as true morphogens since they can induce the formation of the organized complex structures that constitute the embryonic axis.

关键词：胚泡层/药物作用胚泡层/超微结构鸡胚/药物作用鸡胚/胚胎学培养基条件性/药理学培养基无血清/药理学表皮生长因子/药理学成纤维细胞生长因子2/药理学转化生长因子β/药理学维甲酸/药理学爪蟾属动物

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重组人表皮生长因子对植皮创面成活的影响

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中国组织工程研究 2003年第4期7卷 676-677页

作者： Long Jianhong(龙剑虹) Zhang Minghua(张明华) Xie Tingho Departmeen of Burns and Plastic Surgery Xiangya Hospital ofZhongnan Univeasity Changshe 410008 Hunan Province China

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Ligand-independent recruitment of SRC-1 to estrogen receptor β through phosphorylation of activation function AF-1

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MOLECULAR CELL 1999年第4期3卷 513-519页

作者： Tremblay, A Tremblay, GB Labrie, F Giguère, V McGill Univ Ctr Hlth Mol Oncol Grp Montreal PQ H3A 1A1 Canada McGill Univ Dept Biochem Montreal PQ H3A 1A1 Canada McGill Univ Dept Med Montreal PQ H3A 1A1 Canada McGill Univ Dept Oncol Montreal PQ H3A 1A1 Canada Univ Laval Med Res Ctr Mol Endocrinol Lab Quebec City PQ G1V 4G2 Canada

The estrogen receptors (ERs) alpha and beta possess a constitutive N-terminal activation function (AF-1) whose activity can be modulated by kinase signaling pathways. We demonstrate here that phosphorylation of AF-1 by MAP kinase (MAPK) leads to the recruitment of steroid receptor coactivator-1 (SRC-1) by ERP in vitro. Enhancement of the interaction between SRC-1 and ER beta AF-1 is also observed in vivo in cells either treated with EGF or expressing activated Ras. Two serine residues in ER beta AF-1, of which one is contained within a motif present in other steroid receptors, are critical for physical interaction with SRC-1 and transcriptional activation. Our results establish a role for nuclear receptor phosphorylation in the recruitment of SRC-1 and provide a molecular basis for ligand-independent activation by ER beta via the MAPK pathway.

关键词：氨基酸序列 COS细胞表皮生长因子/药理学雌激素受体β 基因表达调控/遗传学基因报告组蛋白酰基转移酶配体分子序列数据突变磷酰化受体雌激素/遗传学受体雌激素/代谢受体干扰素/代谢信号传导转录因子/代谢转染动物小鼠

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Generation of constitutively active p90 ribosomal S6 kinase in vivo.: Implications for the mitogen-activated protein kinase-activated protein kinase family. (vol 274, pg 22135, 1999)

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JOURNAL OF BIOLOGICAL CHEMISTRY 1999年第48期274卷 34506-34506页

作者： Poteet-Smith, CE Smith, JA Lannigan, DA Freed, TA Sturgill, TW DepartmentofMedicine HowardHughesMedicalInstituteUniversityofVirginiaCharlottesvilleVirginia22908USA.

p90 ribosomal S6 kinases (RSKs), containing two distinct kinase catalytic domains, are phosphorylated and activated by extracellular signal-regulated kinase (ERK). The amino-terminal kinase domain (NTD) of RSK phosphorylates exogenous substrates, whereas the carboxyl-terminal kinase domain (CTD) autophosphorylates Ser-386. A conserved putative autoinhibitory alpha helix is present in the carboxyl-terminal tail of the RSK isozymes (^697HLVKGAMAATYSALNR^712 of RSK2). Here, we demonstrate that truncation (Δα) or mutation (Y707A) of this helix in RSK2 resulted in constitutive activation of the CTD. In vivo, both mutants enhanced basal Ser-386 autophosphorylation by the CTD above that of wild type (WT). The enhanced Ser-386 autophosphorylation was attributed to disinhibition of the CTD because a CTD dead mutation (K451A) eliminated Ser-386 autophosphorylation even in conjunction with Δα and Y707A. Constitutive activity of the CTD appears to enhance NTD activity even in the absence of ERK phosphorylation because basal phosphorylation of S6 peptide by Δα and Y707A was ~4-fold above that of WT. A RSK phosphorylation motif antibody detected a 140-kDa protein (pp140) that was phosphorylated upon epidermal growth factor or insulin treatment. Ectopic expression of Δα or Y707A resulted in increased basal phosphorylation of pp140 compared with that of WT, presenting the possibility that pp140 is a novel RSK substrate. Thus, it is clear that the CTD regulates NTD activity in vivo as well as in vitro.

关键词：氨基酸序列钙-钙调素依赖性蛋白激酶类/代谢催化域细胞培养的仓鼠亚科酶激活表皮生长因子/药理学胰岛素/药理学分子序列数据突变磷酰化蛋白质结构二级核糖体蛋白质S6激酶类/化学核糖体蛋白质S6激酶类/遗传学核糖体蛋白质S6激酶类/代谢核糖体/酶学序列缺失序列同源性氨基酸信号传导动物

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Phosphorylation of the nuclear receptor SF-1 modulates cofactor recruitment: Integration of hormone signaling in reproduction and stress

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MOLECULAR CELL 1999年第4期3卷 521-526页

作者： Hammer, GD Krylova, I Zhang, YX Darimont, BD Simpson, K Weigel, NL Ingraham, HA Univ Calif San Francisco Dept Physiol San Francisco CA 94143 USA Univ Calif San Francisco Dept Med San Francisco CA 94143 USA Univ Calif San Francisco Dept Mol & Cellular Pharmacol San Francisco CA 94143 USA Univ Calif San Francisco Summer Res Training Program San Francisco CA 94143 USA Baylor Coll Med Dept Cell Biol Houston TX 77030 USA

Steroidogenic factor 1 (SF-1) is an orphan nuclear receptor that serves as an essential regulator of many hormone-induced genes in the vertebrate endocrine system. The apparent absence of a SF-1 ligand prompted speculation that this receptor is regulated by alternative mechanisms involving signal transduction pathways. Here we show that maximal SF-1-mediated transcription and interaction with general nuclear receptor cofactors depends on phosphorylation of a single serine residue (Ser-203) located in a major activation domain (AF-1) of the protein. Moreover, phosphorylation-dependent SF-1 activation is likely mediated by the mitogen-activated protein kinase (MAPK) signaling pathway. We propose that this single modification of SF-1 and the subsequent recruitment of nuclear receptor cofactors couple extracellular signals to steroid and peptide hormone synthesis, thereby maintaining dynamic homeostatic responses in stress and reproduction.

关键词：钙-钙调素依赖性蛋白激酶类/代谢 DNA结合蛋白质类/遗传学 DNA结合蛋白质类/代谢表皮生长因子/药理学 fushitarazu转录因子类基因报告同源盒结构域蛋白质类突变核蛋白质类/遗传学核受体共激活因子2 磷酰化蛋白质加工转译后受体胞质和核/代谢阻遏蛋白质类/代谢生殖丝氨酸/代谢信号传导/生理学类固醇生成因子1 转录因子/遗传学转录因子/代谢转染肿瘤细胞培养的人类

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Differential regulation of EGF-like growth factor genes in human keratinocytes

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BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS 1999年第1期265卷 214-221页

作者： Stoll, SW Elder, JT Univ Michigan Dept Dermatol Ann Arbor MI 48109 USA Univ Michigan Dept Radiat Oncol Canc Biol Ann Arbor MI 48109 USA Vet Affairs Hosp Ann Arbor MI USA

ErbB signaling increases protein levels of multiple EGF-like growth factors in epithelial cells, To better understand this process, we examined the effects of EGF receptor stimulation on the transcription and mRNA stability of TGF-alpha, amphiregulin (AR), and heparin-binding EGF-like growth factor (HB-EGF) in human keratinocytes, EGF stimulation increased transcription of TGF-alpha, AR and HB-EGF by 3- to 4-fold within 1 to 2 h, However, AR and HB-EGF mRNA levels peaked at 2 h and then rapidly declined, whereas TGF-alpha transcripts remained elevated for at least 6 h, Actinomycin D decay experiments yielded the rank order of transcript stability TGF-alpha > AR > HB-EGF. Interestingly, ligand treatment appeared to stabilize TGF-alpha and AR mRNAs, whereas NB-EGF transcripts were destabilized, These data demonstrate that gene-specific alterations in gene transcription and mRNA stability play important roles in the temporal regulation of EGF-like growth factor gene expression. (C) 1999 Academic Press.

关键词：细胞核/代谢细胞培养的更生霉素/药理学表皮生长因子/遗传学表皮生长因子/药理学基因表达调控/药物作用糖蛋白类/遗传学生长物质/遗传学胞间信号肽类和蛋白质类角蛋白细胞/细胞学角蛋白细胞/代谢动力学 RNA 信使/遗传学受体表皮生长因子/生理学转录遗传/药物作用转化生长因子α/遗传学转化生长因子α/药理学成年人人类

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Amphiregulin is coordinately expressed with heparin-binding epidermal growth factor-like growth factor in the interstitial smooth muscle of the human prostate

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ENDOCRINOLOGY 1999年第12期140卷 5866-5875页

作者： Adam, RM Borer, JG Williams, BJ Eastham, JA Loughlin, KR Freeman, MR Childrens Hosp Dept Urol Urol Lab Boston MA 02115 USA Harvard Univ Sch Med Dept Surg Boston MA 02115 USA Brigham & Womens Hosp Div Urol Boston MA 02115 USA Louisiana State Univ Med Ctr Dept Urol Shreveport LA 71130 USA

Peptide growth factors have been proposed as mediators of smooth muscle-epithelial cell interactions in the human prostate;however, the identity of these molecules has not been established. In this study, we compared expression levels of messenger RNAs (mRNAs) encoding the epidermal growth factor (EGF) receptor-related receptor tyrosine kinases (ErbB1 through 4), the six EGF receptor ligands, EGF, transforming growth factor (TGF)-alpha, amphiregulin (ARG), HB-EGF, betacellulin, and epiregulin, and the related molecule heregulin-alpha, in a series of 10 prostate tissue specimens. Only EGF showed a disease-specific association, with increased mRNA levels in four of five PCa specimens in comparison to matched normal tissue from the same subject. In contrast, ARG and HB-EGF mRNAs showed a coordinate pattern of expression in 7/10 specimens that was distinct from all other growth factor or receptor genes examined and from mRNAs for prostate specific antigen, the androgen receptor and GAPDH, a housekeeping enzyme. Analysis of an additional series of benign prostatic hyperplasia and prostate cancer specimens from 60 individuals confirmed that ARG and HB-EGF mRNA levels varied in a highly coordinate manner (r = 0.93;P < 0.0001) but showed no association with disease. ARG was immunolocalized largely to interstitial smooth muscle cells (SMC), previously identified as the site of synthesis of IIB-EGF in the prostate, while the cognate ARG and HB-EGF receptor, ErbB1, was localized exclusively to ductal epithelial cells and carcinoma cells. Although ARG was a relatively poor mitogen for Balb/c3T3 cells in comparison to HB-EGF, it was similar in potency to HB-EGF in stimulating human prostate epithelial cell growth, suggesting that prostate epithelia may be a physiologic target for ARG in vivo. Expression of both ARG and KB-EGF mRNAs was induced in cultured prostate SMC by fibroblast growth factor-2, a human prostate SMC mitogen linked to prostate disease. These findings indicate

关键词：细胞分裂/药物作用表皮生长因子/分析表皮生长因子/遗传学表皮生长因子/药理学上皮细胞/药物作用成纤维细胞生长因子2/药理学基因表达调控糖蛋白类/分析糖蛋白类/遗传学糖蛋白类/药理学生长物质/分析生长物质/遗传学生长物质/药理学胞间信号肽类和蛋白质类肌平滑/化学肌平滑/代谢癌基因蛋白质v-erbB/遗传学前列腺/化学前列腺/代谢前列腺肿瘤/代谢 RNA 信使/分析 RNA 信使/代谢逆转录聚合酶链反应人类男(雄)性

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