MEKK1 transduces activin signals in keratinocytes to induce actin stress fiber formation and migration.

Abstract:

:Activins and other members of the transforming growth factor beta family play a critical role in morphological changes of the epidermis that require epithelial cell movement. We investigated the molecular pathways in the transmission of activin signals that lead to actin reorganization and epithelial cell migration. We found that activins cause the activation of RhoA but not of Rac and CDC42, leading to MEKK1-dependent phosphorylation of JNK and transcription factor c-Jun. Through a RhoA-independent mechanism, the activins also induce p38 activity in keratinocytes from wild-type but not from MEKK1-deficient mice. Although neither pathway is dependent on Smad activation, the MEKK1-mediated JNK and p38 activities are both essential for activin-stimulated and transcription-dependent keratinocyte migration. Only JNK is involved in transcription-independent actin stress fiber formation, which needs also the activity of ROCK. Because ROCK is required for JNK activation by RhoA and its overexpression leads to MEKK1 activation, we propose a RhoA-ROCK-MEKK1-JNK pathway and a MEKK1-p38 pathway as Smad-independent mechanisms in the transmission of activin signals. Together, these pathways lead to the control of actin cytoskeleton reorganization and epithelial cell migration, contributing to the physiologic and pathological effects of activins on epithelial morphogenesis.

journal_name

Mol Cell Biol

authors

Zhang L,Deng M,Parthasarathy R,Wang L,Mongan M,Molkentin JD,Zheng Y,Xia Y

doi

10.1128/MCB.25.1.60-65.2005

subject

Has Abstract

pub_date

2005-01-01 00:00:00

pages

60-5

issue

1

eissn

0270-7306

issn

1098-5549

pii

25/1/60

journal_volume

25

pub_type

杂志文章
  • Multiple properties of the splicing repressor SRp38 distinguish it from typical SR proteins.

    abstract::The SR protein SRp38 is a general splicing repressor that is activated by dephosphorylation during mitosis and in response to heat shock. Here we describe experiments that provide insights into the mechanism by which SRp38 functions in splicing repression. We first show that SRp38 redistributes and colocalizes with sn...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章

    doi:10.1128/MCB.25.18.8334-8343.2005

    authors: Shin C,Kleiman FE,Manley JL

    更新日期:2005-09-01 00:00:00

  • Three sea urchin actin genes show different patterns of expression: muscle specific, embryo specific, and constitutive.

    abstract::The expression of three different actin genes in the sea urchin, Strongylocentrotus purpuratus, was monitored in embryos and adult tissues by using untranslated mRNA sequences as specific hybridization probes. Three distinct patterns of expression were found: muscle specific, embryo specific, and constitutive (i.e., p...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章

    doi:10.1128/mcb.4.5.840

    authors: Garcia R,Paz-Aliaga B,Ernst SG,Crain WR Jr

    更新日期:1984-05-01 00:00:00

  • The role and fate of DNA ends for homologous recombination in embryonic stem cells.

    abstract::We have analyzed the gene-targeting frequencies and recombination products generated by a series of vectors which target the hprt locus in embryonic stem cells and found the existence of alternative pathways that depend on the location of the double-strand break within the vector. A double-strand break in the targetin...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章

    doi:10.1128/mcb.12.6.2464

    authors: Hasty P,Rivera-Pérez J,Bradley A

    更新日期:1992-06-01 00:00:00

  • Heterogeneous nuclear RNA promotes synthesis of (2',5')oligoadenylate and is cleaved by the (2',5')oligoadenylate-activated endoribonuclease.

    abstract::Heterogeneous nuclear RNA contains double-stranded regions that are not found in mRNA and that may serve as recognition elements for processing enzymes. The double-stranded regions of heterogeneous nuclear RNA prepared from HeLa cells promoted the synthesis of (2',5')oligoadenylate [(2',5')oligo(A) or (2'5')An] when i...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章

    doi:10.1128/mcb.2.2.154

    authors: Nilsen TW,Maroney PA,Robertson HD,Baglioni C

    更新日期:1982-02-01 00:00:00

  • Cardiomyopathy in Irx4-deficient mice is preceded by abnormal ventricular gene expression.

    abstract::To define the role of Irx4, a member of the Iroquois family of homeobox transcription factors in mammalian heart development and function, we disrupted the murine Irx4 gene. Cardiac morphology in Irx4-deficient mice (designated Irx4(Delta ex2/Delta ex2)) was normal during embryogenesis and in early postnatal life. Adu...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章

    doi:10.1128/MCB.21.5.1730-1736.2001

    authors: Bruneau BG,Bao ZZ,Fatkin D,Xavier-Neto J,Georgakopoulos D,Maguire CT,Berul CI,Kass DA,Kuroski-de Bold ML,de Bold AJ,Conner DA,Rosenthal N,Cepko CL,Seidman CE,Seidman JG

    更新日期:2001-03-01 00:00:00

  • A transcriptional insulator element, the su(Hw) binding site, protects a chromosomal DNA replication origin from position effects.

    abstract::Eukaryotic chromosomes are organized into domains of activity for both transcription and DNA replication. Transcriptional "border," or "insulator," elements have been implicated in mediating the organization of transcriptional domains. However, the DNA sequence elements which might demarcate domains of DNA replication...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章

    doi:10.1128/mcb.17.4.2202

    authors: Lu L,Tower J

    更新日期:1997-04-01 00:00:00

  • Alterations of gene structure in ethyl methane sulfonate-induced mutants of mammalian cells.

    abstract::To determine the types of alterations in gene structure induced by DNA-alkylating agents, we analyzed the restriction enzyme cleavage patterns of adenine phosphoribosyltransferase gene sequences in mutant strains of Chinese hamster ovary cells deficient in this enzyme. Base pair changes as detected by loss of restrict...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章

    doi:10.1128/mcb.2.11.1459

    authors: Meuth M,Arrand JE

    更新日期:1982-11-01 00:00:00

  • Transcription mediated by NFAT is highly inducible in effector CD4+ T helper 2 (Th2) cells but not in Th1 cells.

    abstract::Transcriptional factors of the NFAT family play an important role in regulating the expression of several cytokine genes during the immune response, such as the genes for interleukin 2 (IL-2) and IL-4, among others. Upon antigen stimulation, precursor CD4+ T helper (pTh) cells proliferate and differentiate into two po...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章

    doi:10.1128/mcb.17.3.1522

    authors: Rincón M,Flavell RA

    更新日期:1997-03-01 00:00:00

  • A 12-base-pair sequence is an essential element of the ribosomal gene terminator in Xenopus laevis.

    abstract::rRNA transcription in Xenopus laevis terminates near a 7-base-pair (bp) conserved sequence (T3 box) located 200 bp upstream of the site of transcription initiation for the adjacent gene promoter. We present evidence here that a 12-bp element containing the T3 box is an essential part of the terminator. Using an oocyte...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章

    doi:10.1128/mcb.7.5.1900

    authors: Labhart P,Reeder RH

    更新日期:1987-05-01 00:00:00

  • The (6;9) chromosome translocation, associated with a specific subtype of acute nonlymphocytic leukemia, leads to aberrant transcription of a target gene on 9q34.

    abstract::The specific (6;9)(p23;q34) chromosomal translocation is associated with a defined subtype of acute nonlymphocytic leukemia (ANLL). The 9q34 breakpoint is located at the telomeric side of the c-abl gene. Through a combination of chromosome jumping, long-range mapping, and chromosome walking, the chromosome 9 breakpoin...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章

    doi:10.1128/mcb.10.8.4016

    authors: von Lindern M,Poustka A,Lerach H,Grosveld G

    更新日期:1990-08-01 00:00:00

  • Critical binding and regulatory interactions between Ras and Raf occur through a small, stable N-terminal domain of Raf and specific Ras effector residues.

    abstract::Genetic and biochemical evidence suggests that the Ras protooncogene product regulates the activation of the Raf kinase pathway, leading to the proposal that Raf is a direct mitogenic effector of activated Ras. Here we report the use of a novel competition assay to measure in vitro the relative affinity of the c-Raf-1...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章

    doi:10.1128/mcb.14.8.5318

    authors: Chuang E,Barnard D,Hettich L,Zhang XF,Avruch J,Marshall MS

    更新日期:1994-08-01 00:00:00

  • Phosphoinositide 3-kinase catalytic subunit deletion and regulatory subunit deletion have opposite effects on insulin sensitivity in mice.

    abstract::Studies ex vivo have shown that phosphoinositide 3-kinase (PI3K) activity is necessary but not sufficient for insulin-stimulated glucose uptake. Unexpectedly, mice lacking either of the PI3K regulatory subunits p85alpha or p85beta exhibit increased insulin sensitivity. The insulin hypersensitivity is particularly unex...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章

    doi:10.1128/MCB.25.5.1596-1607.2005

    authors: Brachmann SM,Ueki K,Engelman JA,Kahn RC,Cantley LC

    更新日期:2005-03-01 00:00:00

  • Nucleolar KKE/D repeat proteins Nop56p and Nop58p interact with Nop1p and are required for ribosome biogenesis.

    abstract::Different point mutations in the nucleolar protein fibrillarin (Nop1p in Saccharomyces cerevisiae) can inhibit different steps in ribosome synthesis. A screen for mutations that are synthetically lethal (sl) with the nop1-5 allele, which inhibits pre-rRNA processing, identified NOP56. An independent sl mutation screen...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章

    doi:10.1128/mcb.17.12.7088

    authors: Gautier T,Bergès T,Tollervey D,Hurt E

    更新日期:1997-12-01 00:00:00

  • Recruitment of the extracellular signal-regulated kinase/ribosomal S6 kinase signaling pathway to the NFATc4 transcription activation complex.

    abstract::Integration of protein kinases into transcription activation complexes influences the magnitude of gene expression. The nuclear factor of activated T cells (NFAT) group of proteins are critical transcription factors that direct gene expression in immune and nonimmune cells. A balance of phosphotransferase activity is ...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章

    doi:10.1128/MCB.25.3.907-920.2005

    authors: Yang TT,Xiong Q,Graef IA,Crabtree GR,Chow CW

    更新日期:2005-02-01 00:00:00

  • The yeast alpha 2 protein can repress transcription by RNA polymerases I and II but not III.

    abstract::The alpha 2 protein of the yeast Saccharomyces cerevisiae normally represses a set of cell-type-specific genes (the a-specific genes) that are transcribed by RNA polymerase II. In this study, we determined whether alpha 2 can affect transcription by other RNA polymerases. We find that alpha 2 can repress transcription...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章

    doi:10.1128/mcb.13.7.4029

    authors: Herschbach BM,Johnson AD

    更新日期:1993-07-01 00:00:00

  • Phosphorylation of Jak2 on Ser(523) inhibits Jak2-dependent leptin receptor signaling.

    abstract::The leptin receptor, LRb, and other cytokine receptors are devoid of intrinsic enzymatic activity and rely upon the activity of constitutively associated Jak family tyrosine kinases to mediate intracellular signaling. In order to clarify mechanisms by which Jak2, the cognate LRb-associated Jak kinase, is regulated and...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章

    doi:10.1128/MCB.01589-05

    authors: Ishida-Takahashi R,Rosario F,Gong Y,Kopp K,Stancheva Z,Chen X,Feener EP,Myers MG Jr

    更新日期:2006-06-01 00:00:00

  • Cyclin-dependent kinase 1-mediated Bcl-xL/Bcl-2 phosphorylation acts as a functional link coupling mitotic arrest and apoptosis.

    abstract::Despite detailed knowledge of the components of the spindle assembly checkpoint, a molecular explanation of how cells die after prolonged spindle checkpoint activation, and thus how microtubule inhibitors and other antimitotic drugs ultimately elicit their lethal effects, has yet to emerge. Mitotically arrested cells ...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章

    doi:10.1128/MCB.00882-09

    authors: Terrano DT,Upreti M,Chambers TC

    更新日期:2010-02-01 00:00:00

  • ShcA regulates thymocyte proliferation through specific transcription factors and a c-Abl-dependent signaling axis.

    abstract::Signaling via the pre-T-cell receptor (pre-TCR), along with associated signals from Notch and chemokine receptors, regulates the β-selection checkpoint that operates on CD4(-) CD8(-) doubly negative (DN) thymocytes. Since many hematopoietic malignancies arise at the immature developmental stages of lymphocytes, unders...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章

    doi:10.1128/MCB.01084-14

    authors: Trampont PC,Zhang L,Giles AJ,Walk SF,Gu JJ,Pendergast AM,Ravichandran KS

    更新日期:2015-04-01 00:00:00

  • The nematode eukaryotic translation initiation factor 4E/G complex works with a trans-spliced leader stem-loop to enable efficient translation of trimethylguanosine-capped RNAs.

    abstract::Eukaryotic mRNA translation begins with recruitment of the 40S ribosome complex to the mRNA 5' end through the eIF4F initiation complex binding to the 5' m(7)G-mRNA cap. Spliced leader (SL) RNA trans splicing adds a trimethylguanosine (TMG) cap and a sequence, the SL, to the 5' end of mRNAs. Efficient translation of T...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章

    doi:10.1128/MCB.01437-09

    authors: Wallace A,Filbin ME,Veo B,McFarland C,Stepinski J,Jankowska-Anyszka M,Darzynkiewicz E,Davis RE

    更新日期:2010-04-01 00:00:00

  • Identification of candidate angiogenic inhibitors processed by matrix metalloproteinase 2 (MMP-2) in cell-based proteomic screens: disruption of vascular endothelial growth factor (VEGF)/heparin affin regulatory peptide (pleiotrophin) and VEGF/Connective

    abstract::Matrix metalloproteinases (MMPs) exert both pro- and antiangiogenic functions by the release of cytokines or proteolytically generated angiogenic inhibitors from extracellular matrix and basement membrane remodeling. In the Mmp2-/- mouse neovascularization is greatly reduced, but the mechanistic aspects of this remain...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章

    doi:10.1128/MCB.00821-07

    authors: Dean RA,Butler GS,Hamma-Kourbali Y,Delbé J,Brigstock DR,Courty J,Overall CM

    更新日期:2007-12-01 00:00:00

  • Cell cycle-dependent phosphorylation of C/EBPbeta mediates oncogenic cooperativity between C/EBPbeta and H-RasV12.

    abstract::CCAAT/enhancer binding protein beta (C/EBPbeta) is a widely expressed transcription factor whose activity is regulated by oncogenic Ha-RasV12 signaling. C/EBPbeta is essential for the development of mouse skin tumors containing Ras mutations and can cooperate with RasV12 to transform NIH 3T3 cells. Here we have invest...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章

    doi:10.1128/MCB.24.17.7380-7391.2004

    authors: Shuman JD,Sebastian T,Kaldis P,Copeland TD,Zhu S,Smart RC,Johnson PF

    更新日期:2004-09-01 00:00:00

  • SU6656, a selective src family kinase inhibitor, used to probe growth factor signaling.

    abstract::The use of small-molecule inhibitors to study molecular components of cellular signal transduction pathways provides a means of analysis complementary to currently used techniques, such as antisense, dominant-negative (interfering) mutants and constitutively activated mutants. We have identified and characterized a sm...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章

    doi:10.1128/mcb.20.23.9018-9027.2000

    authors: Blake RA,Broome MA,Liu X,Wu J,Gishizky M,Sun L,Courtneidge SA

    更新日期:2000-12-01 00:00:00

  • The ARID family transcription factor bright is required for both hematopoietic stem cell and B lineage development.

    abstract::Bright/Arid3a has been characterized both as an activator of immunoglobulin heavy-chain transcription and as a proto-oncogene. Although Bright expression is highly B lineage stage restricted in adult mice, its expression in the earliest identifiable hematopoietic stem cell (HSC) population suggests that Bright might h...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章

    doi:10.1128/MCB.01448-10

    authors: Webb CF,Bryant J,Popowski M,Allred L,Kim D,Harriss J,Schmidt C,Miner CA,Rose K,Cheng HL,Griffin C,Tucker PW

    更新日期:2011-03-01 00:00:00

  • Dual regulation of c-Myc by p300 via acetylation-dependent control of Myc protein turnover and coactivation of Myc-induced transcription.

    abstract::The c-Myc oncoprotein (Myc) controls cell fate by regulating gene transcription in association with a DNA-binding partner, Max. While Max lacks a transcription regulatory domain, the N terminus of Myc contains a transcription activation domain (TAD) that recruits cofactor complexes containing the histone acetyltransfe...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章

    doi:10.1128/MCB.25.23.10220-10234.2005

    authors: Faiola F,Liu X,Lo S,Pan S,Zhang K,Lymar E,Farina A,Martinez E

    更新日期:2005-12-01 00:00:00

  • pp60c-src in the developing cerebellum.

    abstract::pp60c-src was localized in the cerebellum of developing chicken embryos by immunoperoxidase staining with antisera raised against bacterially expressed pp60v-src. Immunoreactivity (IR) appeared in the cerebellum of the chicken embryos at the time of neuronal differentiation. pp60c-src IR was detected in regions of the...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章

    doi:10.1128/mcb.5.1.27

    authors: Fults DW,Towle AC,Lauder JM,Maness PF

    更新日期:1985-01-01 00:00:00

  • Conditional immortalization of human thyroid epithelial cells: a tool for analysis of oncogene action.

    abstract::To overcome the difficulty of assessing oncogene action in human epithelial cell types, such as thyroid, which have limited proliferative potential in culture, we have explored the use of temperature-sensitive (ts) mutants of simian virus 40 (SV40) early region to create conditionally immortalized epithelial cell line...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章

    doi:10.1128/mcb.10.10.5365

    authors: Wynford-Thomas D,Bond JA,Wyllie FS,Burns JS,Williams ED,Jones T,Sheer D,Lemoine NR

    更新日期:1990-10-01 00:00:00

  • Oxidative stress-responsive transcription factor ATF3 potentially mediates diabetic angiopathy.

    abstract::Previous results of our cDNA microarray analysis to look for genes whose expression level correlates well with in vitro tubulogenesis by NP31 endothelial cells revealed the transcription factor ATF3 known to be responsive to stress such as reactive oxygen species (ROS). Anti-ATF3 small interfering RNA gave an inhibito...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章

    doi:10.1128/MCB.26.3.1087-1097.2006

    authors: Okamoto A,Iwamoto Y,Maru Y

    更新日期:2006-02-01 00:00:00

  • A severely defective TATA-binding protein-TFIIB interaction does not preclude transcriptional activation in vivo.

    abstract::In yeast cells, mutations in the TATA-binding protein (TBP) that disrupt the interaction with the TATA element or with TFIIA can selectively impair the response to acidic activator proteins. We analyzed the transcriptional properties of TBP derivatives in which residues that directly interact with TFIIB were replaced ...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章

    doi:10.1128/mcb.17.3.1336

    authors: Lee M,Struhl K

    更新日期:1997-03-01 00:00:00

  • Three distinct modes of Mec1/ATR and Tel1/ATM activation illustrate differential checkpoint targeting during budding yeast early meiosis.

    abstract::Recombination and synapsis of homologous chromosomes are hallmarks of meiosis in many organisms. Meiotic recombination is initiated by Spo11-induced DNA double-strand breaks (DSBs), whereas chromosome synapsis is mediated by a tripartite structure named the synaptonemal complex (SC). Previously, we proposed that buddi...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章

    doi:10.1128/MCB.00438-13

    authors: Cheng YH,Chuang CN,Shen HJ,Lin FM,Wang TF

    更新日期:2013-08-01 00:00:00

  • Genetic rescue of muscle defects associated with a mutant Drosophila melanogaster tropomyosin allele.

    abstract::We describe a genetic transformation system which should prove useful for investigating tropomyosin assembly and function. Muscle abnormalities associated with a defective tropomyosin allele were corrected by integrating the wild-type gene into germ line chromosomes. The transformation protocol permits application of ...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章

    doi:10.1128/mcb.7.8.2977

    authors: Fyrberg EA,Karlik CC

    更新日期:1987-08-01 00:00:00