Complementation of growth factor receptor-dependent mitogenic signaling by a truncated type I phosphatidylinositol 4-phosphate 5-kinase.


:Substitution of phenylalanine for tyrosine at codon 809 (Y809F) of the human colony-stimulating factor 1 (CSF-1) receptor (CSF-1R) impairs ligand-stimulated tyrosine kinase activity, prevents induction of c-MYC and cyclin D1 genes, and blocks CSF-1-dependent progression through the G1 phase of the cell cycle. We devised an unbiased genetic screen to isolate genes that restore the ability of CSF-1 to stimulate growth in cells that express mutant CSF-1R (Y809F). This screen led us to identify a truncated form of the murine type Ibeta phosphatidylinositol 4-phosphate 5-kinase (mPIP5K-Ibeta). This truncated protein lacks residues 1 to 238 of mPIP5K-Ibeta and is catalytically inactive. When we transfected cells expressing CSF-1R (Y809F) with mPIP5K-Ibeta (delta1-238), CSF-1-dependent induction of c-MYC and cyclin D1 was restored and ligand-dependent cell proliferation was sustained. CSF-1 normally triggers the rapid disappearance of CSF-1R (Y809F) from the cell surface; however, transfection of cells with mPIP5K-Ibeta (delta1-238) stabilized CSF-1R (Y809F) expression on the cell surface, resulting in elevated levels of ligand-activated CSF-1R (Y809F). These results suggest a role for PIP5K-Ibeta in receptor endocytosis and that the truncated enzyme compensated for a mitogenically defective CSF-1R by interfering with this process.


Mol Cell Biol


Davis JN,Rock CO,Cheng M,Watson JB,Ashmun RA,Kirk H,Kay RJ,Roussel MF




Has Abstract


1997-12-01 00:00:00












  • Estrogen receptors recruit SMRT and N-CoR corepressors through newly recognized contacts between the corepressor N terminus and the receptor DNA binding domain.

    abstract::Estrogen receptors (ERs) are hormone-regulated transcription factors that regulate key aspects of reproduction and development. ERs are unusual in that they do not typically repress transcription in the absence of hormone but instead possess otherwise cryptic repressive functions that are revealed upon binding to cert...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章


    authors: Varlakhanova N,Snyder C,Jose S,Hahm JB,Privalsky ML

    更新日期:2010-03-01 00:00:00

  • POU transcription factors Brn-3a and Brn-3b interact with the estrogen receptor and differentially regulate transcriptional activity via an estrogen response element.

    abstract::The estrogen receptor (ER) modulates transcription by forming complexes with other proteins and then binding to the estrogen response element (ERE). We have identified a novel interaction of this receptor with the POU transcription factors Brn-3a and Brn-3b which was independent of ligand binding. By pull-down assays ...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章


    authors: Budhram-Mahadeo V,Parker M,Latchman DS

    更新日期:1998-02-01 00:00:00

  • NAD+-dependent deacetylase Hst1p controls biosynthesis and cellular NAD+ levels in Saccharomyces cerevisiae.

    abstract::Nicotine adenine dinucleotide (NAD(+)) performs key roles in electron transport reactions, as a substrate for poly(ADP-ribose) polymerase and NAD(+)-dependent protein deacetylases. In the latter two processes, NAD(+) is consumed and converted to ADP-ribose and nicotinamide. NAD(+) levels can be maintained by regenerat...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章


    authors: Bedalov A,Hirao M,Posakony J,Nelson M,Simon JA

    更新日期:2003-10-01 00:00:00

  • RAP30/74: a general initiation factor that binds to RNA polymerase II.

    abstract::We have previously shown by affinity chromatography that RAP30 and RAP74 are the mammalian proteins that have the highest affinity for RNA polymerase II. Here we show that RAP30 binds to RAP74 and that the RAP30-RAP74 complex (RAP30/74) is required for accurate initiation by RNA polymerase II. RAP30/74 is required for...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章


    authors: Burton ZF,Killeen M,Sopta M,Ortolan LG,Greenblatt J

    更新日期:1988-04-01 00:00:00

  • The first intron in the human c-abl gene is at least 200 kilobases long and is a target for translocations in chronic myelogenous leukemia.

    abstract::The c-abl protooncogene is unusual in two respects; it has multiple, widely space N-terminal coding exons transcribed by different promoters, and it is the target of the translocations that form the Philadelphia chromosome found in cells of chronic myelogenous leukemia patients. To understand the organization of the g...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章


    authors: Bernards A,Rubin CM,Westbrook CA,Paskind M,Baltimore D

    更新日期:1987-09-01 00:00:00

  • Loss of GATA6 leads to nuclear deformation and aneuploidy in ovarian cancer.

    abstract::A prominent hallmark of most human cancer is aneuploidy, which is a result of the chromosomal instability of cancer cells and is thought to contribute to the initiation and progression of most carcinomas. The developmentally regulated GATA6 transcription factor is commonly lost in ovarian cancer, and the loss of its e...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章


    authors: Capo-chichi CD,Cai KQ,Testa JR,Godwin AK,Xu XX

    更新日期:2009-09-01 00:00:00

  • Saccharomyces cerevisiae Mob1p is required for cytokinesis and mitotic exit.

    abstract::The Saccharomyces cerevisiae mitotic exit network (MEN) is a conserved set of genes that mediate the transition from mitosis to G(1) by regulating mitotic cyclin degradation and the inactivation of cyclin-dependent kinase (CDK). Here, we demonstrate that, in addition to mitotic exit, S. cerevisiae MEN gene MOB1 is req...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章


    authors: Luca FC,Mody M,Kurischko C,Roof DM,Giddings TH,Winey M

    更新日期:2001-10-01 00:00:00

  • Glucose-regulated protein (GRP94 and GRP78) genes share common regulatory domains and are coordinately regulated by common trans-acting factors.

    abstract::We isolated the promoter of the human gene encoding the 94,000-dalton glucose-regulated protein (GRP94). The 5'-flanking region important for its expression was identified by deletion analysis. Comparison of the promoters of the genes for GRP78 and GRP94 derived from human, rat, and chicken cells revealed a common dom...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章


    authors: Chang SC,Erwin AE,Lee AS

    更新日期:1989-05-01 00:00:00

  • The ht beta gene encodes a novel CACCC box-binding protein that regulates T-cell receptor gene expression.

    abstract::A gene encoding a novel CACCC box-binding protein that binds to the promoter region of the human T-cell receptor (TCR) V beta 8.1 gene and the mouse TCR alpha gene silencer has been cloned. This gene, termed ht beta, contains four zinc fingers of the class Cys2-X12-His2 that may be responsible for DNA binding and a hi...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章


    authors: Wang Y,Kobori JA,Hood L

    更新日期:1993-09-01 00:00:00

  • Interleukin-8 Dedifferentiates Primary Human Luminal Cells to Multipotent Stem Cells.

    abstract::During aging, cellular plasticity and senescence play important roles in tissue regeneration and the pathogenesis of different diseases, including cancer. We have recently shown that senescent breast luminal cells can activate their adjacent stromal fibroblasts. In the present report, we present clear evidence that th...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章


    authors: Al-Khalaf HH,Ghebeh H,Wakil SM,Al-Mohanna F,Aboussekhra A

    更新日期:2020-04-13 00:00:00

  • Early expression of yeast genes affected by chemical stress.

    abstract::The variety of environmental stresses is probably the major challenge imposed on transcription activators and the transcriptional machinery. To precisely describe the very early genomic response developed by yeast to accommodate a chemical stress, we performed time course analyses of the modifications of the yeast gen...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章


    authors: Lucau-Danila A,Lelandais G,Kozovska Z,Tanty V,Delaveau T,Devaux F,Jacq C

    更新日期:2005-03-01 00:00:00

  • Partial cleavage of RasGAP by caspases is required for cell survival in mild stress conditions.

    abstract::Tight control of apoptosis is required for proper development and maintenance of homeostasis in multicellular organisms. Cells can protect themselves from potentially lethal stimuli by expressing antiapoptotic factors, such as inhibitors of apoptosis, FLICE (caspase 8)-inhibitory proteins, and members of the Bcl2 fami...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章


    authors: Yang JY,Michod D,Walicki J,Murphy BM,Kasibhatla S,Martin SJ,Widmann C

    更新日期:2004-12-01 00:00:00

  • Yeast protein kinases and the RHO1 exchange factor TUS1 are novel components of the cell integrity pathway in yeast.

    abstract::The PKC1-associated mitogen-activated protein (MAP) kinase pathway of Saccharomyces cerevisiae regulates cell integrity by controlling the actin cytoskeleton and cell wall synthesis. Activation of PKC1 occurs via the GTPase RHO1 and the kinase pair PKH1 and PKH2. Here we report that YPK1 and YPK2, an essential pair of...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章


    authors: Schmelzle T,Helliwell SB,Hall MN

    更新日期:2002-03-01 00:00:00

  • The SET2-RPB1 interaction domain of human RECQ5 is important for transcription-associated genome stability.

    abstract::The conserved RECQ5 DNA helicase is a tumor suppressor in mammalian cells. Defects in RECQ5 lead to the accumulation of spontaneous DNA double-stranded breaks (DSBs) during replication, despite the fact that these cells are proficient in DSB repair by homologous recombination (HR). The reason for this is unknown. Here...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章


    authors: Li M,Xu X,Liu Y

    更新日期:2011-05-01 00:00:00

  • Histone methyltransferase Setd8 represses Gata2 expression and regulates erythroid maturation.

    abstract::Setd8 is the sole histone methyltransferase in mammals capable of monomethylating histone H4 lysine 20 (H4K20me1). Setd8 is expressed at significantly higher levels in erythroid cells than any other cell or tissue type, suggesting that Setd8 has an erythroid-cell-specific function. To test this hypothesis, stable Setd...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章


    authors: Malik J,Getman M,Steiner LA

    更新日期:2015-06-01 00:00:00

  • Selective destabilization of short-lived mRNAs with the granulocyte-macrophage colony-stimulating factor AU-rich 3' noncoding region is mediated by a cotranslational mechanism.

    abstract::The 3' noncoding region element (AUUUA)n specifically targets many short-lived mRNAs for degradation. Although the mechanism by which this sequence functions is not yet understood, a potential link between facilitated mRNA turnover and translation has been implied by the stabilization of cellular mRNAs in the presence...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章


    authors: Aharon T,Schneider RJ

    更新日期:1993-03-01 00:00:00

  • Interaction between PCNA and diubiquitinated Mcm10 is essential for cell growth in budding yeast.

    abstract::The minichromosome maintenance protein 10 (Mcm10) is an evolutionarily conserved factor that is essential for replication initiation and elongation. Mcm10 is part of the eukaryotic replication fork and interacts with a variety of proteins, including the Mcm2-7 helicase and DNA polymerase alpha/primase complexes. A mot...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章


    authors: Das-Bradoo S,Ricke RM,Bielinsky AK

    更新日期:2006-07-01 00:00:00

  • Phospholipase C-delta1 and -delta3 are essential in the trophoblast for placental development.

    abstract::Phosphoinositide-specific phospholipase C (PLC) is a key enzyme in phosphoinositide turnover and is involved in a variety of physiological functions. We analyzed PLCdelta1 knockout mice and found that PLCdelta1 is required for the maintenance of skin homeostasis. However, there were no remarkable abnormalities except ...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章


    authors: Nakamura Y,Hamada Y,Fujiwara T,Enomoto H,Hiroe T,Tanaka S,Nose M,Nakahara M,Yoshida N,Takenawa T,Fukami K

    更新日期:2005-12-01 00:00:00

  • Genome-wide redistribution of meiotic double-strand breaks in Saccharomyces cerevisiae.

    abstract::Meiotic recombination is initiated by the formation of programmed DNA double-strand breaks (DSBs) catalyzed by the Spo11 protein. DSBs are not randomly distributed along chromosomes. To better understand factors that control the distribution of DSBs in budding yeast, we have examined the genome-wide binding and cleava...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章


    authors: Robine N,Uematsu N,Amiot F,Gidrol X,Barillot E,Nicolas A,Borde V

    更新日期:2007-03-01 00:00:00

  • Mcm1 promotes replication initiation by binding specific elements at replication origins.

    abstract::Minichromosome maintenance protein 1 (Mcm1) is required for efficient replication of autonomously replicating sequence (ARS)-containing plasmids in yeast cells. Reduced DNA binding activity in the Mcm1-1 mutant protein (P97L) results in selective initiation of a subset of replication origins and causes instability of ...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章


    authors: Chang VK,Donato JJ,Chan CS,Tye BK

    更新日期:2004-07-01 00:00:00

  • Characterization of productive and sterile transcripts from the immunoglobulin heavy-chain locus: processing of micron and muS mRNA.

    abstract::An analysis of the sizes and sequence content of nuclear RNA transcripts of the heavy-chain locus in two B-cell lymphomas, 70Z/3 and 38C-13, and in selected hybridoma derivatives of 38C has led to the identification of two distinct precursors of the mRNAs encoding the membrane and secretory forms of mu chain. These pr...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章


    authors: Nelson KJ,Haimovich J,Perry RP

    更新日期:1983-07-01 00:00:00

  • Distinct roles for two purified factors in transcription of Xenopus mitochondrial DNA.

    abstract::Transcription of Xenopus laevis mitochondrial DNA (xl-mtDNA) by the mitochondrial RNA polymerase requires a dissociable factor. This factor was purified to near homogeneity and identified as a 40-kDa protein. A second protein implicated in the transcription of mtDNA, the Xenopus homolog of the HMG box protein mtTFA, w...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章


    authors: Antoshechkin I,Bogenhagen DF

    更新日期:1995-12-01 00:00:00

  • The HML mating-type cassette of Saccharomyces cerevisiae is regulated by two separate but functionally equivalent silencers.

    abstract::Mating-type genes resident in the silent cassette HML at the left arm of chromosome III are repressed by the action of four SIR gene products, most likely mediated through two cis-acting sites located on opposite sides of the locus. We showed that deletion of either of these two cis-acting sites from the chromosome di...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章


    authors: Mahoney DJ,Broach JR

    更新日期:1989-11-01 00:00:00

  • Checkpoint-Independent Regulation of Origin Firing by Mrc1 through Interaction with Hsk1 Kinase.

    abstract::Mrc1 is a conserved checkpoint mediator protein that transduces the replication stress signal to the downstream effector kinase. The loss of mrc1 checkpoint activity results in the aberrant activation of late/dormant origins in the presence of hydroxyurea. Mrc1 was also suggested to regulate orders of early origin fir...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章


    authors: Matsumoto S,Kanoh Y,Shimmoto M,Hayano M,Ueda K,Fukatsu R,Kakusho N,Masai H

    更新日期:2017-03-17 00:00:00

  • Cdc1p is an endoplasmic reticulum-localized putative lipid phosphatase that affects Golgi inheritance and actin polarization by activating Ca2+ signaling.

    abstract::In the budding yeast Saccharomyces cerevisiae, mutations in the essential gene CDC1 cause defects in Golgi inheritance and actin polarization. However, the biochemical function of Cdc1p is unknown. Previous work showed that cdc1 mutants accumulate intracellular Ca(2+) and display enhanced sensitivity to the extracellu...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章


    authors: Losev E,Papanikou E,Rossanese OW,Glick BS

    更新日期:2008-05-01 00:00:00

  • Induction of RNA editing at heterologous sites by sequences in apolipoprotein B mRNA.

    abstract::An RNA editing mechanism modifies apolipoprotein B (apo-B) mRNA in the intestine by converting cytosine at nucleotide (nt) 6666 to uracil. To define the sequence requirements for editing, mutant apo-B RNAs were analyzed for the ability to be edited in vitro by enterocyte extracts. Editing was detected by a sensitive a...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章


    authors: Driscoll DM,Lakhe-Reddy S,Oleksa LM,Martinez D

    更新日期:1993-12-01 00:00:00

  • Inhibition of macroautophagy triggers apoptosis.

    abstract::Mammalian cells were observed to die under conditions in which nutrients were depleted and, simultaneously, macroautophagy was inhibited either genetically (by a small interfering RNA targeting Atg5, Atg6/Beclin 1-1, Atg10, or Atg12) or pharmacologically (by 3-methyladenine, hydroxychloroquine, bafilomycin A1, or mone...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章


    authors: Boya P,González-Polo RA,Casares N,Perfettini JL,Dessen P,Larochette N,Métivier D,Meley D,Souquere S,Yoshimori T,Pierron G,Codogno P,Kroemer G

    更新日期:2005-02-01 00:00:00

  • N-cadherin and keratinocyte growth factor receptor mediate the functional interplay between Ki-RASG12V and p53V143A in promoting pancreatic cell migration, invasion, and tissue architecture disruption.

    abstract::The genetic basis of pancreatic ductal adenocarcinoma, which constitutes the most common type of pancreatic malignancy, involves the sequential activation of oncogenes and inactivation of tumor suppressor genes. Among the pivotal genetic alterations are Ki-RAS oncogene activation and p53 tumor suppressor gene inactiva...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章


    authors: Deramaudt TB,Takaoka M,Upadhyay R,Bowser MJ,Porter J,Lee A,Rhoades B,Johnstone CN,Weissleder R,Hingorani SR,Mahmood U,Rustgi AK

    更新日期:2006-06-01 00:00:00

  • Interaction of a mitogen-activated protein kinase signaling module with the neuronal protein JIP3.

    abstract::The c-Jun NH(2)-terminal kinase (JNK) group of mitogen-activated protein kinases (MAPKs) is activated in response to the treatment of cells with inflammatory cytokines and by exposure to environmental stress. JNK activation is mediated by a protein kinase cascade composed of a MAPK kinase and a MAPK kinase kinase. Her...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章


    authors: Kelkar N,Gupta S,Dickens M,Davis RJ

    更新日期:2000-02-01 00:00:00

  • Effect of 5-azacytidine on gene expression in marrow stromal cells.

    abstract::When exposed to 5-azacytidine, marrow stromal cells from active long-term marrow cultures and cell lines derived from simian virus 40-transformed stromal cells rapidly upregulated c-abl and interleukin-6 transcripts while downregulating the expression of collagen I, a major matrix protein. Similar effects occurred wit...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章


    authors: Andrews DF 3rd,Nemunaitis J,Tompkins C,Singer JW

    更新日期:1989-06-01 00:00:00