The erbB-2 mitogenic signaling pathway: tyrosine phosphorylation of phospholipase C-gamma and GTPase-activating protein does not correlate with erbB-2 mitogenic potency.


:The erbB-2 gene product, gp185erbB-2, unlike the structurally related epidermal growth factor (EGF) receptor (EGFR), exhibits constitutive kinase and transforming activity. We used a chimeric EGFR/erbB-2 expression vector to compare the mitogenic signaling pathway of the erbB-2 kinase with that of the EGFR, at similar levels of expression, in response to EGF stimulation. The EGFR/erbB-2 chimera was significantly more active in inducing DNA synthesis than the EGFR when either was expressed in NIH 3T3 cells. Analysis of biochemical pathways implicated in signal transduction by growth factor receptors indicated that both phospholipase C type gamma (PLC-gamma) and the p21ras GTPase-activating protein (GAP) are substrates for the erbB-2 kinase in NIH 3T3 fibroblasts. However, under conditions in which activation of the erbB-2 kinase induced DNA synthesis at least fivefold more efficiently than the EGFR, the levels of erbB-2- or EGFR-induced tyrosine phosphorylation of PLC-gamma and GAP were comparable. In addition, the stoichiometry of tyrosine phosphorylation of these putative substrates by erbB-2 appeared to be at least an order of magnitude lower than that induced by platelet-derived growth factor receptors at comparable levels of mitogenic potency. Thus, our results indicate that differences in tyrosine phosphorylation of PLC-gamma and GAP do not account for the differences in mitogenic activity of the erbB-2 kinase compared with either the EGFR or platelet-derived growth factor receptor in NIH 3T3 fibroblasts.


Mol Cell Biol


Fazioli F,Kim UH,Rhee SG,Molloy CJ,Segatto O,Di Fiore PP




Has Abstract


1991-04-01 00:00:00












  • Inhibition of chicken embryo lens differentiation and lens junction formation in culture by pp60v-src.

    abstract::A culture system was developed which permitted the differentiation of chicken lens epithelial cells to lentoid bodies which contained several cell layers, accumulated high levels of delta-crystallin, and produced extensive gap junctions. This differentiation process was prevented when the cells were infected with a te...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章


    authors: Menko AS,Boettiger D

    更新日期:1988-04-01 00:00:00

  • Internuclear transfer of genetic information in kar1-1/KAR1 heterokaryons in Saccharomyces cerevisiae.

    abstract::Heterokaryons of Saccharomyces cerevisiae have been constructed utilizing the kar1-1 mutation, which prevents nuclear fusion during conjugation (J. Conde and G. Fink, Proc. Natl. Acad. Sci. U.S.A. 73:3651-3655, 1976). Each heterokaryon contained two haploid nuclei that were marked on several chromosomes. They segregat...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章


    authors: Dutcher SK

    更新日期:1981-03-01 00:00:00

  • Hypersensitivity of aryl hydrocarbon receptor-deficient mice to lipopolysaccharide-induced septic shock.

    abstract::Aryl hydrocarbon receptor (AhR), a ligand-activated transcription factor, is known to mediate a wide variety of pharmacological and toxicological effects caused by polycyclic aromatic hydrocarbons. Recent studies have revealed that AhR is involved in the normal development and homeostasis of many organs. Here, we demo...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章


    authors: Sekine H,Mimura J,Oshima M,Okawa H,Kanno J,Igarashi K,Gonzalez FJ,Ikuta T,Kawajiri K,Fujii-Kuriyama Y

    更新日期:2009-12-01 00:00:00

  • Functional interaction between p53, the TATA-binding protein (TBP), andTBP-associated factors in vivo.

    abstract::The transcriptional activator p53 is known to interact with components of the general transcription factor TFIID in vitro. To examine the relevance of these associations to transcriptional activation in vivo, plasmids expressing a p53-GAL4 chimera and Drosophila TATA-binding protein (dTBP) were transfected into Drosop...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章


    authors: Farmer G,Colgan J,Nakatani Y,Manley JL,Prives C

    更新日期:1996-08-01 00:00:00

  • Stably denatured regions in chromosomal DNA from the cdc2 Saccharomyces cerevisiae cell cycle mutant.

    abstract::DNA isolated from Saccharomyces cerevisiae strains carrying temperature-sensitive mutations in the CDC2 gene after incubation at the restrictive temperature contains multiple stably denatured regions 200 to 700 base pairs long. These regions are probably stabilized by a DNA-binding protein. They are found in both repl...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章


    authors: Conrad MN,Newlon CS

    更新日期:1983-09-01 00:00:00

  • Can ACG serve as an initiation codon for protein synthesis in eucaryotic cells?

    abstract::An ACG codon, which replaces the AUG codon used to initiate the synthesis of bacteriophage T7 gene 0.3 protein, was shown to function as a low-efficiency initiation codon in a wheat germ cell-free protein-synthesizing system. ...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章


    authors: Anderson CW,Buzash-Pollert E

    更新日期:1985-12-01 00:00:00

  • The aryl hydrocarbon receptor mediates degradation of estrogen receptor alpha through activation of proteasomes.

    abstract::2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) and other aryl hydrocarbon receptor (AhR) ligands suppress 17beta-estradiol (E)-induced responses in the rodent uterus and mammary tumors and in human breast cancer cells. Treatment of ZR-75, T47D, and MCF-7 human breast cancer cells with TCDD induces proteasome-dependent deg...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章


    authors: Wormke M,Stoner M,Saville B,Walker K,Abdelrahim M,Burghardt R,Safe S

    更新日期:2003-03-01 00:00:00

  • Microcell-mediated cotransfer of genes specifying methotrexate resistance, emetine sensitivity, and chromate sensitivity with Chinese hamster chromosome 2.

    abstract::Many selectable mutants of somatic Chinese hamster cells have been described, but very few of the mutations have been mapped to specific chromosomes. We have utilized the microcell-mediated gene transfer technique to establish the location of three selectable genetic markers on chromosome 2 of Chinese hamster. Microce...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章


    authors: Worton R,Duff C,Flintoff W

    更新日期:1981-04-01 00:00:00

  • RNA Binding by Histone Methyltransferases Set1 and Set2.

    abstract::Histone methylation at H3K4 and H3K36 is commonly associated with genes actively transcribed by RNA polymerase II (RNAPII) and is catalyzed by Saccharomyces cerevisiae Set1 and Set2, respectively. Here we report that both methyltransferases can be UV cross-linked to RNA in vivo High-throughput sequencing of the bound ...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章


    authors: Sayou C,Millán-Zambrano G,Santos-Rosa H,Petfalski E,Robson S,Houseley J,Kouzarides T,Tollervey D

    更新日期:2017-06-29 00:00:00

  • Endoplasmic reticulum stress-induced formation of transcription factor complex ERSF including NF-Y (CBF) and activating transcription factors 6alpha and 6beta that activates the mammalian unfolded protein response.

    abstract::The levels of molecular chaperones and folding enzymes in the endoplasmic reticulum (ER) are controlled by a transcriptional induction process termed the unfolded protein response (UPR). The mammalian UPR is mediated by the cis-acting ER stress response element (ERSE), the consensus sequence of which is CCAAT-N(9)-CCA...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章


    authors: Yoshida H,Okada T,Haze K,Yanagi H,Yura T,Negishi M,Mori K

    更新日期:2001-02-01 00:00:00

  • Two distinct mechanisms of chromatin interaction by the Isw2 chromatin remodeling complex in vivo.

    abstract::We have previously shown that Saccharomyces cerevisiae Isw2 complex slides nucleosomes to remodel chromatin in vivo. Our data suggested a model in which Isw2 complex binds the histone octamer and DNA separately to generate the force necessary for nucleosome movement. Here we find that the histone H4 "basic patch" is t...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章


    authors: Fazzio TG,Gelbart ME,Tsukiyama T

    更新日期:2005-11-01 00:00:00

  • Role of transcription factor NFAT in glucose and insulin homeostasis.

    abstract::Compromised immunoregulation contributes to obesity and complications in metabolic pathogenesis. Here, we demonstrate that the nuclear factor of activated T cell (NFAT) group of transcription factors contributes to glucose and insulin homeostasis. Expression of two members of the NFAT family (NFATc2 and NFATc4) is ind...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章


    authors: Yang TT,Suk HY,Yang X,Olabisi O,Yu RY,Durand J,Jelicks LA,Kim JY,Scherer PE,Wang Y,Feng Y,Rossetti L,Graef IA,Crabtree GR,Chow CW

    更新日期:2006-10-01 00:00:00

  • Mutations in the zinc fingers of ADR1 that change the specificity of DNA binding and transactivation.

    abstract::ADR1 is a yeast transcription factor that contains two zinc fingers of the Cys-2-His-2 (C2H2) class. Mutations that change the specificity of DNA binding of ADR1 to its target site, upstream activation sequence 1 (UAS1), have been identified at three positions in the first zinc finger. Mutations Arg-115 to Gln, His-11...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章


    authors: Thukral SK,Morrison ML,Young ET

    更新日期:1992-06-01 00:00:00

  • The complete sequence of the mouse skeletal alpha-actin gene reveals several conserved and inverted repeat sequences outside of the protein-coding region.

    abstract::The complete nucleotide sequence of a genomic clone encoding the mouse skeletal alpha-actin gene has been determined. This single-copy gene codes for a protein identical in primary sequence to the rabbit skeletal alpha-actin. It has a large intron in the 5'-untranslated region 12 nucleotides upstream from the initiato...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章


    authors: Hu MC,Sharp SB,Davidson N

    更新日期:1986-01-01 00:00:00

  • SDC25, a CDC25-like gene which contains a RAS-activating domain and is a dispensable gene of Saccharomyces cerevisiae.

    abstract::In the yeast Saccharomyces cerevisiae, the CDC25 gene product activates adenylate cyclase through RAS1 and RAS2 gene products. We have recently described the cloning of a DNA fragment which suppresses the cdc25 mutation but not ras1, ras2, or cdc35 mutations. This fragment contains a 5'-truncated open reading frame wh...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章


    authors: Damak F,Boy-Marcotte E,Le-Roscouet D,Guilbaud R,Jacquet M

    更新日期:1991-01-01 00:00:00

  • Generation of rac3 null mutant mice: role of Rac3 in Bcr/Abl-caused lymphoblastic leukemia.

    abstract::Numerous studies indirectly implicate Rac GTPases in cancer. To investigate if Rac3 contributes to normal or malignant cell function, we generated rac3 null mutants through gene targeting. These mice were viable, fertile, and lacked an obvious external phenotype. This shows Rac3 function is dispensable for embryonic d...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章


    authors: Cho YJ,Zhang B,Kaartinen V,Haataja L,de Curtis I,Groffen J,Heisterkamp N

    更新日期:2005-07-01 00:00:00

  • Peroxisome proliferator-activated receptor alpha regulates a microRNA-mediated signaling cascade responsible for hepatocellular proliferation.

    abstract::Activation of peroxisome proliferator-activated receptor alpha (PPARalpha) leads to hepatocellular proliferation and liver carcinomas. The early events mediating these effects are unknown. A novel mechanism by which PPARalpha regulates gene expression and hepatocellular proliferation was uncovered. MicroRNA (miRNA) ex...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章


    authors: Shah YM,Morimura K,Yang Q,Tanabe T,Takagi M,Gonzalez FJ

    更新日期:2007-06-01 00:00:00

  • RNA-mediated gene duplication: the rat preproinsulin I gene is a functional retroposon.

    abstract::Rats and mice have two, equally expressed, nonallelic genes encoding preproinsulin (genes I and II). Cytological hybridization with metaphase chromosomes indicated that both genes reside on rat chromosome I but are approximately 100,000 kilobases apart. In mice the two genes reside on two different chromosomes. DNA se...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章


    authors: Soares MB,Schon E,Henderson A,Karathanasis SK,Cate R,Zeitlin S,Chirgwin J,Efstratiadis A

    更新日期:1985-08-01 00:00:00

  • Composition and architecture of the Schizosaccharomyces pombe Rad18 (Smc5-6) complex.

    abstract::The rad18 gene of Schizosaccharomyces pombe is an essential gene that is involved in several different DNA repair processes. Rad18 (Smc6) is a member of the structural maintenance of chromosomes (SMC) family and, together with its SMC partner Spr18 (Smc5), forms the core of a high-molecular-weight complex. We show her...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章


    authors: Sergeant J,Taylor E,Palecek J,Fousteri M,Andrews EA,Sweeney S,Shinagawa H,Watts FZ,Lehmann AR

    更新日期:2005-01-01 00:00:00

  • Isolation of rsp-1, a novel cDNA capable of suppressing v-Ras transformation.

    abstract::Using an expression cloning assay, we have isolated a novel cDNA, referred to as rsp-1, which suppresses the v-Ras-transformed phenotype. When introduced into NIH 3T3 fibroblasts under the control of a metallothionein promoter, rsp-1 confers resistance to v-Ras, but not to v-Mos or v-Src, and inhibits growth of the ce...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章


    authors: Cutler ML,Bassin RH,Zanoni L,Talbot N

    更新日期:1992-09-01 00:00:00

  • Exon and intron sequences, respectively, repress and activate splicing of a fibroblast growth factor receptor 2 alternative exon.

    abstract::Two alternative exons, BEK and K-SAM, code for part of the ligand binding site of fibroblast growth factor receptor 2. Splicing of these exons is mutually exclusive, and the choice between them is made in a tissue-specific manner. We identify here pre-mRNA sequences involved in controlling splicing of the K-SAM exon. ...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章


    authors: Del Gatto F,Breathnach R

    更新日期:1995-09-01 00:00:00

  • Molecular analysis of the SNF2/SWI2 protein family member MOT1, an ATP-driven enzyme that dissociates TATA-binding protein from DNA.

    abstract::MOT1 is an essential Saccharomyces cerevisiae protein and a member of the SNF2/SWI2 family of ATPases. MOT1 functions by removing TATA-binding protein (TBP) from DNA, and as a consequence, MOT1 can regulate transcription both in vitro and in vivo. Here we describe the in vivo and in vitro activities of MOT1 deletion a...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章


    authors: Auble DT,Wang D,Post KW,Hahn S

    更新日期:1997-08-01 00:00:00

  • Nuclear factor I X deficiency causes brain malformation and severe skeletal defects.

    abstract::The transcription factor family of nuclear factor I (NFI) proteins is encoded by four closely related genes: Nfia, Nfib, Nfic, and Nfix. A potential role for NFI proteins in regulating developmental processes has been implicated by their specific expression pattern during embryonic development and by analysis of NFI-d...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章


    authors: Driller K,Pagenstecher A,Uhl M,Omran H,Berlis A,Gründer A,Sippel AE

    更新日期:2007-05-01 00:00:00

  • Mouse germ cell-less as an essential component for nuclear integrity.

    abstract::A mouse homologue of the Drosophila melanogaster germ cell-less (mgcl-1) gene is expressed ubiquitously, and its gene product is localized to the nuclear envelope based on its binding to LAP2 beta (lamina-associated polypeptide 2 beta). To elucidate the role of mgcl-1, we analyzed two mutant mouse lines that lacked mg...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章


    authors: Kimura T,Ito C,Watanabe S,Takahashi T,Ikawa M,Yomogida K,Fujita Y,Ikeuchi M,Asada N,Matsumiya K,Okuyama A,Okabe M,Toshimori K,Nakano T

    更新日期:2003-02-01 00:00:00

  • p300 requires its histone acetyltransferase activity and SRC-1 interaction domain to facilitate thyroid hormone receptor activation in chromatin.

    abstract::We have characterized the mechanism by which coactivator p300 facilitates transcriptional activation mediated by the heterodimer of thyroid hormone (T3) receptor and 9-cis retinoid acid receptor (TR-RXR) in the context of chromatin. We demonstrate that, while p300 can enhance the transcriptional activation mediated by...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章


    authors: Li J,O'Malley BW,Wong J

    更新日期:2000-03-01 00:00:00

  • Proliferative activation of quiescent Rat-1A cells by delta FosB.

    abstract::Fos and Jun transcription factors are induced during the normal course of the proliferative response of quiescent cells to serum or to growth factors. We have shown that delta FosB, an alternatively spliced form of FosB, is formed as rapidly as FosB in serum-stimulated Rat-1A cells. Although delta FosB lacks the C-ter...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章


    authors: Nakabeppu Y,Oda S,Sekiguchi M

    更新日期:1993-07-01 00:00:00

  • A link between secretion and pre-mRNA processing defects in Saccharomyces cerevisiae and the identification of a novel splicing gene, RSE1.

    abstract::Secretory proteins in eukaryotic cells are transported to the cell surface via the endoplasmic reticulum (ER) and the Golgi apparatus by membrane-bounded vesicles. We screened a collection of temperature-sensitive mutants of Saccharomyces cerevisiae for defects in ER-to-Golgi transport. Two of the genes identified in ...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章


    authors: Chen EJ,Frand AR,Chitouras E,Kaiser CA

    更新日期:1998-12-01 00:00:00

  • p53 inhibits DNA replication in vitro in a DNA-binding-dependent manner.

    abstract::The p53 tumor suppressor gene product is a sequence-specific DNA-binding protein that is necessary for the G1 arrest of many cell types. Consistent with its role as a cell cycle checkpoint factor, p53 has been shown to be capable of both transcriptional activation and repression. Here we show a new potential role for ...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章


    authors: Miller SD,Farmer G,Prives C

    更新日期:1995-12-01 00:00:00

  • Tyrosyl and cyclic AMP-dependent protein kinase activities in BHK cells that express viral pp60src.

    abstract::Protein kinase activities were measured in Rous sarcoma virus-infected baby hamster kidney (BHK) cells that express v-src (BHK [v-src]) and compared with those of revertant and control BHK cells. We observed about a fivefold-higher tyrosine phosphorylating activity in BHK (v-src) cell extracts, which was due to src bu...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章


    authors: Clinton GM,Roskoski R Jr

    更新日期:1984-05-01 00:00:00

  • CTCF controls expression and chromatin architecture of the human major histocompatibility complex class II locus.

    abstract::The major histocompatibility complex class II (MHC-II) locus includes a dense cluster of genes that function to initiate immune responses. Expression of insulator CCCTC binding factor (CTCF) was found to be required for expression of all MHC class II genes associated with antigen presentation. Ten CTCF sites that divi...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章


    authors: Majumder P,Boss JM

    更新日期:2010-09-01 00:00:00