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 Bioljournal_title
Molecular and cellular biologyauthors
Shams I,Rohmann E,Eswarakumar VP,Lew ED,Yuzawa S,Wollnik B,Schlessinger J,Lax Idoi
10.1128/MCB.00544-07subject
Has Abstractpub_date
2007-10-01 00:00:00pages
6903-12issue
19eissn
0270-7306issn
1098-5549pii
MCB.00544-07journal_volume
27pub_type
杂志文章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
更新日期:2001-08-01 00:00:00
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
更新日期:2007-08-01 00:00:00
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
更新日期:2000-05-01 00:00:00
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
更新日期:2000-12-01 00:00:00
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
更新日期:2007-05-01 00:00:00
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
更新日期:1993-06-01 00:00:00
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
更新日期:1997-12-01 00:00:00
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
更新日期:2006-08-01 00:00:00
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
更新日期:2009-10-01 00:00:00
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
更新日期:1989-05-01 00:00:00
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
更新日期:1990-01-01 00:00:00
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
更新日期:2007-12-01 00:00:00
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
更新日期:1993-06-01 00:00:00
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
更新日期:1989-08-01 00:00:00
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
更新日期:1994-12-01 00:00:00
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
更新日期:2012-07-01 00:00:00
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
更新日期:1995-07-01 00:00:00
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
更新日期:2006-04-01 00:00:00
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
更新日期:2015-01-01 00:00:00
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
更新日期:2015-11-01 00:00:00
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
更新日期:2006-09-01 00:00:00
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
更新日期:2001-11-01 00:00:00
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
更新日期:1986-06-01 00:00:00
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
更新日期:1985-08-01 00:00:00
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
更新日期:2015-03-01 00:00:00
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
更新日期:1992-10-01 00:00:00
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
更新日期:1983-08-01 00:00:00
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
更新日期:2002-04-01 00:00:00
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
更新日期:2009-08-01 00:00:00
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
更新日期:1990-11-01 00:00:00