G protein-coupled receptor-mediated mitogen-activated protein kinase activation through cooperation of Galpha(q) and Galpha(i) signals.


:G protein-coupled receptors (GPCRs) have been shown to stimulate extracellular regulated kinases (ERKs) through a number of linear pathways that are initiated by G(q/11) or G(i) proteins. We studied signaling to the ERK cascade by receptors that simultaneously activate both G protein subfamilies. In HEK293T cells, bradykinin B(2) receptor (B(2)R)-induced stimulation of ERK2 and transcriptional activity of Elk1 are dependent on Galpha(q)-mediated protein kinase C (PKC) and on Galpha(i)-induced Ras activation, while they are independent of Gbetagamma subunits, phosphatidylinositol 3-kinase, and tyrosine kinases. Similar results were obtained with m(1) and m(3) muscarinic receptors in HEK293T cells and with the B(2)R in human and mouse fibroblasts, indicating a general mechanism in signaling toward the ERK cascade. Furthermore, the bradykinin-induced activation of ERK is strongly reduced in Galpha(q/11)-deficient fibroblasts. In addition, we found that constitutively active mutants of Galpha(q/11) or Galpha(i) proteins alone poorly stimulate ERK2, whereas a combination of both led to synergistic effects. We conclude that dually coupled GPCRs require a cooperation of Galpha(i)- and G(q/11)-mediated pathways for efficient stimulation of the ERK cascade. Cooperative signaling by multiple G proteins thus might represent a novel concept implicated in the regulation of cellular responses by GPCRs.


Mol Cell Biol


Blaukat A,Barac A,Cross MJ,Offermanns S,Dikic I




Has Abstract


2000-09-01 00:00:00












  • Progenitor stage-specific activity of a cis-acting double GATA motif for Gata1 gene expression.

    abstract::GATA1 is a master regulator of erythropoiesis, expression of which is regulated by multiple discrete cis-acting elements. In this study, we examine the activity of a promoter-proximal double GATA (dbGATA) motif, using a Gata1 bacterial artificial chromosome (BAC)-transgenic green fluorescent protein (GFP) reporter (G1...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章


    authors: Moriguchi T,Suzuki M,Yu L,Takai J,Ohneda K,Yamamoto M

    更新日期:2015-03-01 00:00:00

  • Loss of Androgen-Regulated MicroRNA 1 Activates SRC and Promotes Prostate Cancer Bone Metastasis.

    abstract::Bone metastasis is the hallmark of progressive and castration-resistant prostate cancers. MicroRNA 1 (miR-1) levels are decreased in clinical samples of primary prostate cancer and further reduced in metastases. SRC has been implicated as a critical factor in bone metastasis, and here we show that SRC is a direct targ...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章


    authors: Liu YN,Yin J,Barrett B,Sheppard-Tillman H,Li D,Casey OM,Fang L,Hynes PG,Ameri AH,Kelly K

    更新日期:2015-06-01 00:00:00

  • A combinatorial code for gene expression generated by transcription factor Bach2 and MAZR (MAZ-related factor) through the BTB/POZ domain.

    abstract::Bach2 is a B-cell- and neuron-specific transcription repressor that forms heterodimers with the Maf-related oncoproteins. We show here that Bach2 activates transcription by interacting with its novel partner MAZR. MAZR was isolated by the yeast two-hybrid screen using the BTB/POZ domain of Bach2 as bait. Besides the B...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章


    authors: Kobayashi A,Yamagiwa H,Hoshino H,Muto A,Sato K,Morita M,Hayashi N,Yamamoto M,Igarashi K

    更新日期:2000-03-01 00:00:00

  • Protein kinase C-theta isoenzyme selective stimulation of the transcription factor complex AP-1 in T lymphocytes.

    abstract::T-lymphocyte stimulation requires activation of several protein kinases, including the major phorbol ester receptor protein kinase C (PKC), ultimately leading to induction of lymphokines, such as interleukin-2 (IL-2). The revelant PKC isoforms which are involved in the activation cascades of nuclear transcription fact...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章


    authors: Baier-Bitterlich G,Uberall F,Bauer B,Fresser F,Wachter H,Grunicke H,Utermann G,Altman A,Baier G

    更新日期:1996-04-01 00:00:00

  • Repression of quiescence-specific polypeptides in chicken heart mesenchymal cells transformed by Rous sarcoma virus.

    abstract::Chicken heart mesenchymal cells do not proliferate in medium of physiological composition containing plasma (S. Balk, Proc. Natl. Acad. Sci. USA 77:6606-6610, 1980). To understand the molecular events involved in cell quiescence and in the initiation of cell division under physiological conditions, we examined the dif...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章


    authors: Bédard PA,Balk SD,Gunther HS,Morisi A,Erikson RL

    更新日期:1987-04-01 00:00:00

  • Multiple interferon regulatory factor and NF-κB sites cooperate in mediating cell-type- and maturation-specific activation of the human CD83 promoter in dendritic cells.

    abstract::CD83 is one of the best-known surface markers for fully mature dendritic cells (mature DCs), and its cell-type- and maturation-specific regulation makes the CD83 promoter an interesting tool for the genetic modulation of DCs. To determine the mechanisms regulating this DC- and maturation-specific CD83 expression, chro...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章


    authors: Stein MF,Lang S,Winkler TH,Deinzer A,Erber S,Nettelbeck DM,Naschberger E,Jochmann R,Stürzl M,Slany RK,Werner T,Steinkasserer A,Knippertz I

    更新日期:2013-04-01 00:00:00

  • Pro-B-cell-specific transcription and proapoptotic function of protein kinase Ceta.

    abstract::Using a subtractive cloning scheme on cDNA prepared from primary pro-B and pre-B cells, we identified several genes whose products regulate apoptosis. We further characterized one of these genes, encoding protein kinase Ceta (PKCeta). PKCeta transcripts were readily detected in pro-B cells but were absent in pre-B cel...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章


    authors: Morrow TA,Muljo SA,Zhang J,Hardwick JM,Schlissel MS

    更新日期:1999-08-01 00:00:00

  • The Drosophila polycomb group protein Psc contacts ph and Pc through specific conserved domains.

    abstract::The Polycomb group proteins are transcriptional repressors that are thought to act through multimeric nuclear complexes. We show that ph and Psc coprecipitate with Pc from nuclear extracts. We have analyzed the domains required for the association of Psc with ph and Pc by using the yeast two-hybrid system and an in vi...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章


    authors: Kyba M,Brock HW

    更新日期:1998-05-01 00:00:00

  • A PEX7-centered perspective on the peroxisomal targeting signal type 2-mediated protein import pathway.

    abstract::Peroxisomal matrix proteins are synthesized on cytosolic ribosomes and transported to the organelle by shuttling receptors. Matrix proteins containing a type 1 signal are carried to the peroxisome by PEX5, whereas those harboring a type 2 signal are transported by a PEX5-PEX7 complex. The pathway followed by PEX5 duri...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章


    authors: Rodrigues TA,Alencastre IS,Francisco T,Brites P,Fransen M,Grou CP,Azevedo JE

    更新日期:2014-08-01 00:00:00

  • A conserved alpha-helical motif mediates the interaction of Sp1-like transcriptional repressors with the corepressor mSin3A.

    abstract::Sp1-like proteins are defined by three highly homologous C(2)H(2) zinc finger motifs that bind GC-rich sequences found in the promoters of a large number of genes essential for mammalian cell homeostasis. Here we report that TIEG2, a transforming growth factor beta-inducible Sp1-like protein with antiproliferative fun...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章


    authors: Zhang JS,Moncrieffe MC,Kaczynski J,Ellenrieder V,Prendergast FG,Urrutia R

    更新日期:2001-08-01 00:00:00

  • Dax1 binds to Oct3/4 and inhibits its transcriptional activity in embryonic stem cells.

    abstract::Embryonic stem (ES) cells are pluripotent cells derived from the inner cell mass of blastocysts. Transcription factor Oct3/4 is an indispensable factor in the self-renewal of ES cells. In this study, we searched for a protein that would interact with Oct3/4 in ES cells and identified an orphan nuclear hormone receptor...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章


    authors: Sun C,Nakatake Y,Akagi T,Ura H,Matsuda T,Nishiyama A,Koide H,Ko MS,Niwa H,Yokota T

    更新日期:2009-08-01 00:00:00

  • DNA sequence-directed nucleosome reconstitution on 5S RNA genes of Xenopus laevis.

    abstract::Nucleosomes were reconstituted in vitro with several singly end-labeled restriction fragments derived from a cloned somatic-type 5S RNA gene of Xenopus laevis and purified nucleosome core particles from Xenopus cultured cells or chicken erythrocytes. Nucleosome locations were determined by digestion of the reconstitut...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章


    authors: Gottesfeld JM

    更新日期:1987-05-01 00:00:00

  • Estrogen-inducible binding of a nuclear factor to the vitellogenin upstream region.

    abstract::The estrogen-dependent binding of a protein to the upstream region of the chicken vitellogenin gene was detected by using in vivo dimethyl sulfate, genomic DNase I, and in vitro exonuclease III footprinting. The site is located between base pairs -848 and -824, and its sequence resembles that of the nuclear factor I b...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章


    authors: Bakker O,Philipsen JN,Hennis BC,Ab G

    更新日期:1988-10-01 00:00:00

  • Expression of a human cytochrome p450 in yeast permits analysis of pathways for response to and repair of aflatoxin-induced DNA damage.

    abstract::Aflatoxin B1 (AFB1) is a human hepatotoxin and hepatocarcinogen produced by the mold Aspergillus flavus. In humans, AFB1 is primarily bioactivated by cytochrome P450 1A2 (CYP1A2) and 3A4 to a genotoxic epoxide that forms N7-guanine DNA adducts. A series of yeast haploid mutants defective in DNA repair and cell cycle c...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章


    authors: Guo Y,Breeden LL,Zarbl H,Preston BD,Eaton DL

    更新日期:2005-07-01 00:00:00

  • Concerted action of the transcriptional activators REB1, RAP1, and GCR1 in the high-level expression of the glycolytic gene TPI.

    abstract::In Saccharomyces cerevisiae, the TPI gene product, triosephosphate isomerase, makes up about 2% of the soluble cellular protein. Using in vitro and in vivo footprinting techniques, we have identified four binding sites for three factors in the 5' noncoding region of TPI: a REB1-binding site located at positions -401 t...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章


    authors: Scott EW,Baker HV

    更新日期:1993-01-01 00:00:00

  • Cellular senescence requires CDK5 repression of Rac1 activity.

    abstract::Cellular senescence is a tumor-suppressive process characterized by an irreversible cell cycle exit, a unique morphology, and expression of senescence-associated beta-galactosidase (SA-beta-Gal). We report here a role for CDK5 in induction of senescent cytoskeletal changes. CDK5 activation is upregulated in senescing ...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章


    authors: Alexander K,Yang HS,Hinds PW

    更新日期:2004-04-01 00:00:00

  • Determination of the spectrum of mutations induced by defined-wavelength solar UVB (313-nm) radiation in mammalian cells by use of a shuttle vector.

    abstract::Mutations induced by UVB (313-nm) radiation, a wavelength in the region of peak effectiveness for sunlight-induced skin cancer in humans, have been analyzed at the sequence level in simian cells by using a plasmid shuttle vector (pZ189). We find that significant differences exist between the types of mutations induced...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章


    authors: Keyse SM,Amaudruz F,Tyrrell RM

    更新日期:1988-12-01 00:00:00

  • Inhibition of phorbol ester-receptor binding by a factor from human serum.

    abstract::The inhibition of receptor binding of [3H]phorbol-12,13-dibutyrate (PDBu) by a factor from human serum was characterized. The serum factor inhibited [3H]PDBu binding in intact monolayer cultures of the rat embryo cell line CREF N and in a subcellular system containing membranes from these cells. Inhibition occurred at...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章


    authors: Horowitz AD,Greenebaum E,Nicolaides M,Woodward K,Weinstein IB

    更新日期:1982-05-01 00:00:00

  • The endothelial receptor tyrosine kinase Tie1 activates phosphatidylinositol 3-kinase and Akt to inhibit apoptosis.

    abstract::Tie1 is an orphan receptor tyrosine kinase that is expressed almost exclusively in endothelial cells and that is required for normal embryonic vascular development. Genetic studies suggest that Tie1 promotes endothelial cell survival, but other studies have suggested that the Tie1 kinase has little to no activity, and...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章


    authors: Kontos CD,Cha EH,York JD,Peters KG

    更新日期:2002-03-01 00:00:00

  • Kinds of mutations formed when a shuttle vector containing adducts of benzo[a]pyrene-7,8-diol-9,10-epoxide replicates in COS7 cells.

    abstract::We have investigated the kinds of mutations induced when a shuttle vector containing covalently bound residues of the (+/-)-7 beta,8 alpha-dihydroxy-9 alpha,10 alpha-epoxy-7,8,9,10-tetrahydrobenzo[a]pyrene (BPDE) replicates in the monkey kidney cell line COS7. The target for detecting mutations was the 200-base pair g...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章


    authors: Yang JL,Maher VM,McCormick JJ

    更新日期:1987-03-01 00:00:00

  • Retinoblastoma tumor suppressor protein signals through inhibition of cyclin-dependent kinase 2 activity to disrupt PCNA function in S phase.

    abstract::The retinoblastoma tumor suppressor protein (RB) is a negative regulator of the cell cycle that inhibits both G(1) and S-phase progression. While RB-mediated G(1) inhibition has been extensively studied, the mechanism utilized for S-phase inhibition is unknown. To delineate the mechanism through which RB inhibits DNA ...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章


    authors: Sever-Chroneos Z,Angus SP,Fribourg AF,Wan H,Todorov I,Knudsen KE,Knudsen ES

    更新日期:2001-06-01 00:00:00

  • Alteration of NCoR corepressor splicing in mice causes increased body weight and hepatosteatosis without glucose intolerance.

    abstract::Alternative mRNA splicing is an important means of diversifying function in higher eukaryotes. Notably, both NCoR and SMRT corepressors are subject to alternative mRNA splicing, yielding a series of distinct corepressor variants with highly divergent functions. Normal adipogenesis is associated with a switch in corepr...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章


    authors: Goodson ML,Young BM,Snyder CA,Schroeder AC,Privalsky ML

    更新日期:2014-11-15 00:00:00

  • DNA sequences required for specific and efficient initiation of transcription at the polyoma virus early promoter.

    abstract::The 5'-flanking DNA sequences involved in the specific and efficient transcription of the polyoma virus early region have been investigated. Sequence requirements for efficient in vivo expression differed from those in vitro. Deletion of DNA located between 200 and 400 base pairs before the principal cap sites severel...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章


    authors: Jat P,Novak U,Cowie A,Tyndall C,Kamen R

    更新日期:1982-07-01 00:00:00

  • Differential recognition of liganded and unliganded thyroid hormone receptor by retinoid X receptor regulates transcriptional repression.

    abstract::Thyroid hormone receptor (TR) functions as part of multiprotein complexes that also include retinoid X receptor (RXR) and transcriptional coregulators. We have found that both the TR CoR box and ninth heptad are required for RXR interaction and in turn for interaction with corepressor proteins N-CoR and SMRT. Remarkab...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章


    authors: Zhang J,Zamir I,Lazar MA

    更新日期:1997-12-01 00:00:00

  • Conditional deletion of focal adhesion kinase leads to defects in ventricular septation and outflow tract alignment.

    abstract::To examine a role for focal adhesion kinase (FAK) in cardiac morphogenesis, we generated a line of mice with a conditional deletion of FAK in nkx2-5-expressing cells (herein termed FAKnk mice). FAKnk mice died shortly after birth, likely resulting from a profound subaortic ventricular septal defect and associated mala...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章


    authors: Hakim ZS,DiMichele LA,Doherty JT,Homeister JW,Beggs HE,Reichardt LF,Schwartz RJ,Brackhan J,Smithies O,Mack CP,Taylor JM

    更新日期:2007-08-01 00:00:00

  • The forkhead transcription factor FOXM1 controls cell cycle-dependent gene expression through an atypical chromatin binding mechanism.

    abstract::There are nearly 50 forkhead (FOX) transcription factors encoded in the human genome and, due to sharing a common DNA binding domain, they are all thought to bind to similar DNA sequences. It is therefore unclear how these transcription factors are targeted to specific chromatin regions to elicit specific biological e...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章


    authors: Chen X,Müller GA,Quaas M,Fischer M,Han N,Stutchbury B,Sharrocks AD,Engeland K

    更新日期:2013-01-01 00:00:00

  • Positive autoregulation of the yeast transcription factor Pdr3p, which is involved in control of drug resistance.

    abstract::Simultaneous resistance to an array of drugs with different cytotoxic activities is a property of Saccharomyces cerevisiae, in which the protein Pdr3p has recently been shown to play a role as a transcriptional regulator. We provide evidence that the yeast PDR3 gene, which encodes a zinc finger transcription factor im...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章


    authors: Delahodde A,Delaveau T,Jacq C

    更新日期:1995-08-01 00:00:00

  • Identification of a matrix-associated region 5' of an immunoglobulin heavy chain variable region gene.

    abstract::In the accompanying report (C. F. Webb, C. Das, S. Eaton, K. Calame, and P. Tucker, Mol. Cell. Biol. 11:5197-5205, 1991), we characterize B-cell-specific protein-DNA interactions at -500 and -200 bp upstream of the mu immunoglobulin heavy chain promoter whose abundances were increased by interleukin-5 plus antigen. Be...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章


    authors: Webb CF,Das C,Eneff KL,Tucker PW

    更新日期:1991-10-01 00:00:00

  • Definition of essential sequences and functional equivalence of elements downstream of the adenovirus E2A and the early simian virus 40 polyadenylation sites.

    abstract::In addition to the highly conserved AATAAA sequence, there is a requirement for specific sequences downstream of polyadenylic acid [poly(A)] cleavage sites to generate correct mRNA 3' termini. Previous experiments demonstrated that 35 nucleotides downstream of the E2A poly(A) site were sufficient but 20 nucleotides we...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章


    authors: Hart RP,McDevitt MA,Ali H,Nevins JR

    更新日期:1985-11-01 00:00:00

  • The Brn-2 transcription factor links activated BRAF to melanoma proliferation.

    abstract::Malignant melanoma, an aggressive and increasingly common cancer, is characterized by a strikingly high rate (70%) of mutations in BRAF, a key component of the mitogen-activated protein (MAP) kinase signaling pathway. How signaling events downstream from BRAF affect the underlying program of gene expression is poorly ...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章


    authors: Goodall J,Wellbrock C,Dexter TJ,Roberts K,Marais R,Goding CR

    更新日期:2004-04-01 00:00:00