Lacrimo-auriculo-dento-digital syndrome is caused by reduced activity of the fibroblast growth factor 10 (FGF10)-FGF receptor 2 signaling pathway.

Abstract:

:Lacrimo-auriculo-dento-digital (LADD) syndrome is characterized by abnormalities in lacrimal and salivary glands, in teeth, and in the distal limbs. Genetic studies have implicated heterozygous mutations in fibroblast growth factor 10 (FGF10) and in FGF receptor 2 (FGFR2) in LADD syndrome. However, it is not clear whether LADD syndrome mutations (LADD mutations) are gain- or loss-of-function mutations. In order to reveal the molecular mechanism underlying LADD syndrome, we have compared the biological properties of FGF10 LADD and FGFR2 LADD mutants to the activities of their normal counterparts. These experiments show that the biological activities of three different FGF10 LADD mutants are severely impaired by different mechanisms. Moreover, haploinsufficiency caused by defective FGF10 mutants leads to LADD syndrome. We also demonstrate that the tyrosine kinase activities of FGFR2 LADD mutants expressed in transfected cells are strongly compromised. Since tyrosine kinase activity is stimulated by ligand-induced receptor dimerization, FGFR2 LADD mutants may also exert a dominant inhibitory effect on signaling via wild-type FGFR2 expressed in the same cell. These experiments underscore the importance of signal strength in mediating biological responses and that relatively small changes in receptor signaling may influence the outcome of developmental processes in cells or organs that do not possess redundant signaling pathway.

journal_name

Mol Cell Biol

authors

Shams I,Rohmann E,Eswarakumar VP,Lew ED,Yuzawa S,Wollnik B,Schlessinger J,Lax I

doi

10.1128/MCB.00544-07

subject

Has Abstract

pub_date

2007-10-01 00:00:00

pages

6903-12

issue

19

eissn

0270-7306

issn

1098-5549

pii

MCB.00544-07

journal_volume

27

pub_type

杂志文章
  • G(alpha)11 signaling through ARF6 regulates F-actin mobilization and GLUT4 glucose transporter translocation to the plasma membrane.

    abstract::The action of insulin to recruit the intracellular GLUT4 glucose transporter to the plasma membrane of 3T3-L1 adipocytes is mimicked by endothelin 1, which signals through trimeric G(alpha)q or G(alpha)11 proteins. Here we report that murine G(alpha)11 is most abundant in fat and that expression of the constitutively ...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章

    doi:10.1128/MCB.21.15.5262-5275.2001

    authors: Bose A,Cherniack AD,Langille SE,Nicoloro SM,Buxton JM,Park JG,Chawla A,Czech MP

    更新日期:2001-08-01 00:00:00

  • Distinct endocytic mechanisms of CD22 (Siglec-2) and Siglec-F reflect roles in cell signaling and innate immunity.

    abstract::Sialic acid-binding immunoglobulin-like lectins (siglecs) are predominately expressed on immune cells. They are best known as regulators of cell signaling mediated by cytoplasmic tyrosine motifs and are increasingly recognized as receptors for pathogens that bear sialic acid-containing glycans. Most siglec proteins un...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章

    doi:10.1128/MCB.00383-07

    authors: Tateno H,Li H,Schur MJ,Bovin N,Crocker PR,Wakarchuk WW,Paulson JC

    更新日期:2007-08-01 00:00:00

  • Facilitated nucleocytoplasmic shuttling of the Ran binding protein RanBP1.

    abstract::The Ran binding protein RanBP1 is localized to the cytosol of interphase cells. A leucine-rich nuclear export signal (NES) near the C terminus of RanBP1 is essential to maintain this distribution. We now show that RanBP1 accumulates in nuclei of cells treated with the export inhibitor, leptomycin B, and collapse of th...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章

    doi:10.1128/mcb.20.10.3510-3521.2000

    authors: Plafker K,Macara IG

    更新日期:2000-05-01 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

  • Mechanisms of checkpoint kinase Rad53 inactivation after a double-strand break in Saccharomyces cerevisiae.

    abstract::In Saccharomyces cerevisiae, double-strand breaks (DSBs) activate DNA checkpoint pathways that trigger several responses including a strong G(2)/M arrest. We have previously provided evidence that the phosphatases Ptc2 and Ptc3 of the protein phosphatase 2C type are required for DNA checkpoint inactivation after a DSB...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章

    doi:10.1128/MCB.00863-06

    authors: Guillemain G,Ma E,Mauger S,Miron S,Thai R,Guérois R,Ochsenbein F,Marsolier-Kergoat MC

    更新日期:2007-05-01 00:00:00

  • Multiple SWI6-dependent cis-acting elements control SWI4 transcription through the cell cycle.

    abstract::The Saccharomyces cerevisiae SWI4 gene encodes an essential transcription factor which controls gene expression at the G1/S transition of the cell cycle. SWI4 transcription itself is cell cycle regulated, and this periodicity is crucial for the normal cell cycle regulation of HO and at least two of the G1 cyclins. Sin...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章

    doi:10.1128/mcb.13.6.3792

    authors: Foster R,Mikesell GE,Breeden L

    更新日期:1993-06-01 00:00:00

  • Transcriptional activation by TFIIB mutants that are severely impaired in interaction with promoter DNA and acidic activation domains.

    abstract::Biochemical experiments indicate that the general transcription factor IIB (TFIIB) can interact directly with acidic activation domains and that activators can stimulate transcription by increasing recruitment of TFIIB to promoters. For promoters at which recruitment of TFIIB to promoters is limiting in vivo, one woul...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章

    doi:10.1128/mcb.17.12.6794

    authors: Chou S,Struhl K

    更新日期:1997-12-01 00:00:00

  • Proteasomal inhibition attenuates transcriptional activity of hypoxia-inducible factor 1 (HIF-1) via specific effect on the HIF-1alpha C-terminal activation domain.

    abstract::The ubiquitin-proteasome pathway (UPP) is involved in regulation of multiple cellular processes. Hypoxia-inducible factor 1 alpha (HIF-1 alpha) is a prototypic target of the UPP and, as such, is stabilized under conditions of proteasomal inhibition. Using carbonic anhydrase IX (CAIX) and vascular endothelial growth fa...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章

    doi:10.1128/MCB.00552-06

    authors: Kaluz S,Kaluzová M,Stanbridge EJ

    更新日期:2006-08-01 00:00:00

  • The HECT-type E3 ubiquitin ligase AIP2 inhibits activation-induced T-cell death by catalyzing EGR2 ubiquitination.

    abstract::E3 ubiquitin ligases, which target specific molecules for proteolytic destruction, have emerged as key regulators of immune functions. Several E3 ubiquitin ligases, including c-Cbl, Cbl-b, GRAIL, Itch, and Nedd4, have been shown to negatively regulate T-cell activation. Here, we report that the HECT-type E3 ligase AIP...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章

    doi:10.1128/MCB.00407-09

    authors: Chen A,Gao B,Zhang J,McEwen T,Ye SQ,Zhang D,Fang D

    更新日期:2009-10-01 00:00:00

  • A transcriptional cascade governs entry into meiosis in Saccharomyces cerevisiae.

    abstract::Two signals activate meiosis in yeast: starvation and expression of the a1 and alpha 2 products of the mating-type locus. Prior studies suggest that these signals stimulate expression of an activator of meiosis, the IME1 (inducer of meiosis) product. We have cloned a gene, IME2, with properties similar to those of IME...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章

    doi:10.1128/mcb.9.5.2142

    authors: Smith HE,Mitchell AP

    更新日期:1989-05-01 00:00:00

  • Developmental regulation of specific protein interactions with an enhancerlike binding site far upstream from the avian very-low-density apolipoprotein II gene.

    abstract::Expression of the avian very-low-density apolipoprotein II (apoVLDLII) gene is completely dependent on estrogen and restricted to the liver. We have identified binding sites for nonhistone nuclear proteins located between -1.96 and -2.61 kilobases. One of these sites, located at -2.6 kilobases (designated site 1), was...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章

    doi:10.1128/mcb.10.1.154

    authors: Hoodless PA,Roy RN,Ryan AK,Haché RJ,Vasa MZ,Deeley RG

    更新日期:1990-01-01 00:00:00

  • Sumoylation of EKLF promotes transcriptional repression and is involved in inhibition of megakaryopoiesis.

    abstract::Erythroid Krüppel-like factor (EKLF [KLF1]) is a transcriptional regulator that plays a critical role within a specific subset of hematopoietic cells, particularly in the erythroid lineage and its immediate precursor, the megakaryocyte-erythroid progenitor (MEP). We find that EKLF is posttranslationally modified by su...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章

    doi:10.1128/MCB.00589-07

    authors: Siatecka M,Xue L,Bieker JJ

    更新日期:2007-12-01 00:00:00

  • Probing keratinocyte and differentiation specificity of the human K5 promoter in vitro and in transgenic mice.

    abstract::Keratins K5 and K14 form the extensive intermediate filament network of mitotically active basal cells in all stratified epithelia. We have explored the regulatory mechanisms governing cell-type-specific and differentiation stage-specific expression of the human K5 gene in transiently transfected keratinocytes in vitr...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章

    doi:10.1128/mcb.13.6.3176

    authors: Byrne C,Fuchs E

    更新日期:1993-06-01 00:00:00

  • Muscle creatine kinase sequence elements regulating skeletal and cardiac muscle expression in transgenic mice.

    abstract::Muscle creatine kinase (MCK) is expressed at high levels only in skeletal and cardiac muscle tissues. Previous in vitro transfection studies of skeletal muscle myoblasts and fibroblasts had identified two MCK enhancer elements and one proximal promoter element, each of which exhibited expression only in differentiated...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章

    doi:10.1128/mcb.9.8.3393

    authors: Johnson JE,Wold BJ,Hauschka SD

    更新日期:1989-08-01 00:00:00

  • Transposition of the yeast retroviruslike element Ty3 is dependent on the cell cycle.

    abstract::Host cell cycle genes provide important functions to retroviruses and retroviruslike elements. To define some of these functions, the cell cycle dependence of transposition of the yeast retroviruslike element Ty3 was examined. Ty3 is unique among retroviruslike elements because of the specificity of its integration, w...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章

    doi:10.1128/mcb.14.12.8229

    authors: Menees TM,Sandmeyer SB

    更新日期:1994-12-01 00:00:00

  • Identification of estrogen receptor β as a SUMO-1 target reveals a novel phosphorylated sumoylation motif and regulation by glycogen synthase kinase 3β.

    abstract::SUMO conjugation has emerged as a dynamic process in regulating protein function. Here we identify estrogen receptor β (ERβ) to be a new target of SUMO-1. ERβ SUMO-1 modification occurs on a unique nonconsensus sumoylation motif which becomes fully competent upon phosphorylation of its contained serine residue, which ...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章

    doi:10.1128/MCB.06624-11

    authors: Picard N,Caron V,Bilodeau S,Sanchez M,Mascle X,Aubry M,Tremblay A

    更新日期:2012-07-01 00:00:00

  • Evidence for impaired retinoic acid receptor-thyroid hormone receptor AF-2 cofactor activity in human lung cancer.

    abstract::Retinoic acid (RA) is required for normal airway epithelial cell growth and differentiation both in vivo and in vitro. One of the earliest events following the exposure of bronchial epithelial cells to RA is the strong induction of RA receptor beta (RAR beta) mRNA. Previous work established that many lung cancer cell ...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章

    doi:10.1128/mcb.15.7.3945

    authors: Moghal N,Neel BG

    更新日期:1995-07-01 00:00:00

  • Subcellular targeting of p33ING1b by phosphorylation-dependent 14-3-3 binding regulates p21WAF1 expression.

    abstract::ING1 is a type II tumor suppressor that affects cell growth, stress signaling, apoptosis, and DNA repair by altering chromatin structure and regulating transcription. Decreased ING1 expression is seen in several human cancers, and mislocalization has been noted in diverse types of cancer cells. Aberrant targeting may,...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章

    doi:10.1128/MCB.26.8.2947-2954.2006

    authors: Gong W,Russell M,Suzuki K,Riabowol K

    更新日期:2006-04-01 00:00:00

  • The major myelin-resident protein PLP is transported to myelin membranes via a transcytotic mechanism: involvement of sulfatide.

    abstract::Myelin membranes are sheet-like extensions of oligodendrocytes that can be considered membrane domains distinct from the cell's plasma membrane. Consistent with the polarized nature of oligodendrocytes, we demonstrate that transcytotic transport of the major myelin-resident protein proteolipid protein (PLP) is a key e...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章

    doi:10.1128/MCB.00848-14

    authors: Baron W,Ozgen H,Klunder B,de Jonge JC,Nomden A,Plat A,Trifilieff E,de Vries H,Hoekstra D

    更新日期:2015-01-01 00:00:00

  • Group IVA Cytosolic Phospholipase A2 Regulates the G2-to-M Transition by Modulating the Activity of Tumor Suppressor SIRT2.

    abstract::The G2-to-M transition (or prophase) checkpoint of the cell cycle is a critical regulator of mitotic entry. SIRT2, a tumor suppressor gene, contributes to the control of this checkpoint by blocking mitotic entry under cellular stress. However, the mechanism underlying both SIRT2 activation and regulation of the G2-to-...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章

    doi:10.1128/MCB.00184-15

    authors: Movahedi Naini S,Sheridan AM,Force T,Shah JV,Bonventre JV

    更新日期:2015-11-01 00:00:00

  • Nup214 is required for CRM1-dependent nuclear protein export in vivo.

    abstract::Nucleoporins mediate transport of macromolecules across the nuclear pore complex, yet the function of many individual nucleoporins is largely unresolved. To address this question, we depleted cells of the cytoplasmic nucleoporins Nup214/CAN and Nup358/RanBP2 by RNA interference. Depletion of Nup214 resulted in codeple...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章

    doi:10.1128/MCB.00342-06

    authors: Hutten S,Kehlenbach RH

    更新日期:2006-09-01 00:00:00

  • Molecular basis for telomere repeat divergence in budding yeast.

    abstract::Telomerase is a ribonucleoprotein enzyme that adds repetitive sequences to the ends of linear chromosomes, thereby counteracting nucleotide loss due to incomplete replication. A short region of the telomerase RNA subunit serves as template for nucleotide addition onto the telomere 3' end. Although Saccharomyces cerevi...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章

    doi:10.1128/MCB.21.21.7277-7286.2001

    authors: Förstemann K,Lingner J

    更新日期:2001-11-01 00:00:00

  • Tissue localization of Drosophila melanogaster ras transcripts during development.

    abstract::Three ras homologs have been identified in Drosophila melanogaster. Here we describe the tissue distribution of their transcripts as analyzed by in situ hybridization. The RNAs of the three genes show a similar distribution at every developmental stage examined. In embryos, the transcripts are uniformly distributed. I...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章

    doi:10.1128/mcb.6.6.2241

    authors: Segal D,Shilo BZ

    更新日期:1986-06-01 00:00:00

  • Topological requirements for homologous recombination among DNA molecules transfected into mammalian cells.

    abstract::Cultured animal cells rearrange foreign DNA very efficiently by homologous recombination. The individual steps that constitute the mechanism(s) of homologous recombination in transfected DNA are as yet undefined. In this study, we examined the topological requirements by using the genome of simian virus 40 (SV40) as a...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章

    doi:10.1128/mcb.5.8.2080

    authors: Wake CT,Vernaleone F,Wilson JH

    更新日期:1985-08-01 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

    doi:10.1128/MCB.01011-14

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

    更新日期:2015-03-01 00:00:00

  • A proposed mechanism for promoter-associated DNA rearrangement events at a variant surface glycoprotein gene expression site.

    abstract::The expressed variant cell surface glycoprotein (VSG) gene of the protozoan parasite Trypanosoma brucei is invariably found at one of several telomeric VSG gene expression sites (ESs). The active ES in variant 118 clone 1 is found on a 1.5-Mb chromosome, and the promoter region is located more than 45 kb upstream of t...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章

    doi:10.1128/mcb.12.10.4784

    authors: Gottesdiener KM,Goriparthi L,Masucci JP,Van der Ploeg LH

    更新日期:1992-10-01 00:00:00

  • Methylation and rearrangement of mouse intracisternal a particle genes in development, aging, and myeloma.

    abstract::Sequences of DNA that hybridize on Southern blots with cloned intracisternal A-particle (IAP) sequences have been examined in genomic DNAs of neonatal mice, livers of adult mice (3, 6, 12, 18, 24, and 26 months old), and the solid myeloma tumor MOPC-315. The isoschizomers HpaII (CCGG or mCCGG) and MspI (CCGG or CmCGG)...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章

    doi:10.1128/mcb.3.8.1371

    authors: Mays-Hoopes LL,Brown A,Huang RC

    更新日期:1983-08-01 00:00:00

  • Analysis of sequence upstream of the endogenous H19 gene reveals elements both essential and dispensable for imprinting.

    abstract::Imprinting of the linked and oppositely expressed mouse H19 and Igf2 genes requires a 2-kb differentially methylated domain (DMD) that is located 2 kb upstream of H19. This element is postulated to function as a methylation-sensitive insulator. Here we test whether an additional sequence 5' of H19 is required for H19 ...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章

    doi:10.1128/mcb.22.8.2450-2462.2002

    authors: Thorvaldsen JL,Mann MR,Nwoko O,Duran KL,Bartolomei MS

    更新日期:2002-04-01 00:00:00

  • Phosphorylation of eukaryotic translation initiation factor 2alpha coordinates rRNA transcription and translation inhibition during endoplasmic reticulum stress.

    abstract::The endoplasmic reticulum (ER) is the major cellular compartment where folding and maturation of secretory and membrane proteins take place. When protein folding needs exceed the capacity of the ER, the unfolded protein response (UPR) pathway modulates gene expression and downregulates protein translation to restore h...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章

    doi:10.1128/MCB.00260-09

    authors: DuRose JB,Scheuner D,Kaufman RJ,Rothblum LI,Niwa M

    更新日期:2009-08-01 00:00:00

  • Repair and recombination of X-irradiated plasmids in Xenopus laevis oocytes.

    abstract::Plasmid DNA substrates were X-irradiated and injected into the nuclei of Xenopus laevis oocytes. After incubation for 20 h, DNA was recovered from the oocytes and analyzed simultaneously for repair and for intermolecular homologous recombination by electrophoresis and bacterial transformation. Oocyte-mediated repair o...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章

    doi:10.1128/mcb.10.11.5849

    authors: Sweigert SE,Carroll D

    更新日期:1990-11-01 00:00:00