Abstract:
: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.
journal_name
Mol Cell Bioljournal_title
Molecular and cellular biologyauthors
Davis JN,Rock CO,Cheng M,Watson JB,Ashmun RA,Kirk H,Kay RJ,Roussel MFdoi
10.1128/mcb.17.12.7398subject
Has Abstractpub_date
1997-12-01 00:00:00pages
7398-406issue
12eissn
0270-7306issn
1098-5549journal_volume
17pub_type
杂志文章abstract::Vascular smooth muscle cells (vSMCs) are key in the regulation of blood pressure and the engagement of vascular pathologies, such as hypertension, arterial remodeling, and neointima formation. The role of the Rac1 GTPase in these cells remains poorly characterized. To clarify this issue, we have utilized genetically e...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/MCB.01066-14
更新日期:2014-12-01 00:00:00
abstract::We have previously described an isolated kinetoplast system from Crithidia fasciculata capable of ATP-dependent replication of kinetoplast DNA minicircles (L. Birkenmeyer and D.S. Ray, J. Biol. Chem. 261: 2362-2368, 1986). We present here the identification of two new minicircle species observed in short pulse-labelin...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.9.1.169
更新日期:1989-01-01 00:00:00
abstract::To study repair of DNA double-strand breaks (DSBs) in mammalian chromosomes, we designed DNA substrates containing a thymidine kinase (TK) gene disrupted by the 18-bp recognition site for yeast endonuclease I-SceI. Some substrates also contained a second defective TK gene sequence to serve as a genetic donor in recomb...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.19.12.8353
更新日期:1999-12-01 00:00:00
abstract::Gap junctional intercellular communication is inhibited in response to tumor promoters and oncogene transformation, suggesting that loss of this function is an important step in tumor formation. To elucidate the molecular mechanisms responsible for this inhibition, we examined the expression of gap junction proteins a...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.11.10.5364
更新日期:1991-10-01 00:00:00
abstract::BUD23 was identified from a bioinformatics analysis of Saccharomyces cerevisiae genes involved in ribosome biogenesis. Deletion of BUD23 leads to severely impaired growth, reduced levels of the small (40S) ribosomal subunit, and a block in processing 20S rRNA to 18S rRNA, a late step in 40S maturation. Bud23 belongs t...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/MCB.01674-07
更新日期:2008-05-01 00:00:00
abstract::Using in vitro replication assays, we compared native with salt-treated simian virus 40 minichromosomes isolated from infected cell nuclei. Minichromosomes from both preparations contain the full complement of nucleosomes, but salt treatment removes histone H1 and a fraction of nonhistone chromatin proteins. Both type...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.13.2.1059
更新日期:1993-02-01 00:00:00
abstract::The 2 micron plasmid of Saccharomyces cerevisiae codes for a site-specific recombinase, the FLP protein, that catalyzes efficient recombination across two 599-base-pair (bp) inverted repeats of the plasmid DNA both in vivo and in vitro. We analyzed the interaction of the purified FLP protein with the target sequences ...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.6.7.2482
更新日期:1986-07-01 00:00:00
abstract::In Schizosaccharomyces pombe, MBF is a DNA-binding complex suspected to activate the transcription of genes necessary for entry into S phase. The MBF complex contains both p85cdc10 and p72res1/sct1. To obtain a better understanding of how the MBF complex regulates gene expression at the G1/S transition, we have perfor...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.15.5.2589
更新日期:1995-05-01 00:00:00
abstract::F9 embryonic teratocarcinoma stem cells differentiate into an epithelial cell type called extraembryonic endoderm when treated with retinoic acid (RA), a derivative of retinol (vitamin A). This differentiation is presumably mediated through the actions of retinoid receptors, the RARs and RXRs. To delineate the functio...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.15.2.843
更新日期:1995-02-01 00:00:00
abstract::YY1 is a multifunctional transcription factor that acts as an activator or repressor in different contexts. YY1 binds to multiple sites in the mouse c-fos promoter, inducing at each site a sharp DNA bend. Binding of YY1 to a site situated between the cyclic AMP response element (CRE) and the TATA box bends the DNA in ...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.15.11.5975
更新日期:1995-11-01 00:00:00
abstract::The coordinated expression of CD4 and CD8 during T-cell development is tightly coupled with the maturation state of the T cell. Additionally, the mutually exclusive expression of these receptors in mature T cells is representative of the functional T-cell subclasses (CD4+ helper T cells versus CD8+ cytotoxic T cells)....
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.14.10.6452
更新日期:1994-10-01 00:00:00
abstract::We have studied the abilities of different transactivation domains to stimulate the initiation and elongation (postinitiation) steps of RNA polymerase II transcription in vivo. Nuclear run-on and RNase protection analyses revealed three classes of activation domains: Sp1 and CTF stimulated initiation (type I); human i...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.16.5.2044
更新日期:1996-05-01 00:00:00
abstract::The HOG (high-osmolarity glycerol) mitogen-activated protein kinase (MAPK) pathway regulates the osmotic stress response in the yeast Saccharomyces cerevisiae. Three type 2C Ser/Thr phosphatases (PTCs), Ptc1, Ptc2, and Ptc3, have been isolated as negative regulators of this pathway. Previously, multicopy expression of...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/MCB.21.1.51-60.2001
更新日期:2001-01-01 00:00:00
abstract::Retrovirus vector infection was used to introduce large numbers of unique genetic markers into tumor cell populations for the purpose of analyzing comparative changes in the clonal composition of metastatic versus that of nonmetastatic tumors during their progressive growth in vivo. The cell lines used were SP1, a non...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.8.8.3143
更新日期:1988-08-01 00:00:00
abstract::The Saccharomyces cerevisiae Cdc42p GTPase interacts with multiple regulators and downstream effectors through an approximately 25-amino-acid effector domain. Four effector domain mutations, Y32K, F37A, D38E, and Y40C, were introduced into Cdc42p and characterized for their effects on these interactions. Each mutant p...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.20.22.8548-8559.2000
更新日期:2000-11-01 00:00:00
abstract::RNA interference (RNAi) in animals, cosuppression in plants, and quelling in fungi are homology-dependent gene silencing mechanisms in which the introduction of either double-stranded RNA (dsRNA) or transgenes induces sequence-specific mRNA degradation. These phenomena share a common genetic and mechanistic basis. The...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.24.6.2536-2545.2004
更新日期:2004-03-01 00:00:00
abstract::The yeast alpha-factor pheromone receptor is a member of the G-protein-coupled receptor family. Limited trypsin digestion of yeast membranes was used to investigate ligand-induced conformational changes in this receptor. The agonist, alpha-factor, accelerated cleavage in the third intracellular loop, whereas the antag...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.16.9.4818
更新日期:1996-09-01 00:00:00
abstract::The RBP-J/Su(H) DNA-binding protein plays a key role in transcriptional regulation by targeting Epstein-Barr virus nuclear antigen 2 (EBNA2) and the intracellular portions of Notch receptors to specific promoters. Using the yeast two-hybrid system, we isolated a LIM-only protein, KyoT, which physically interacts with ...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.18.1.644
更新日期:1998-01-01 00:00:00
abstract::We previously identified a sequence-specific erythroid cell-enriched endoribonuclease (ErEN) activity involved in the turnover of the stable alpha-globin mRNA. We now demonstrate that ErEN activity is regulated by the poly(A) tail. The unadenylated alpha-globin 3' untranslated region (3'UTR) was an efficient substrate...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.20.17.6334-6341.2000
更新日期:2000-09-01 00:00:00
abstract::The genes of the trithorax group (trxG) in Drosophila melanogaster are required to maintain the pattern of homeotic gene expression that is established early in embryogenesis by the transient expression of the segmentation genes. The precise role of each of the diverse trxG members and the functional relationships amo...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.19.2.1159
更新日期:1999-02-01 00:00:00
abstract::Retinoic acid is known to have profound effects on developmental processes. It has been implicated as a putative morphogen in the developing chick limb bud and regenerating amphibian limb blastema and has been demonstrated to have powerful teratogenic effects in mammals, including humans. Recently, three specific reti...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.10.5.2335
更新日期:1990-05-01 00:00:00
abstract::B-myc is a recently described myc gene whose product has not been functionally characterized. The predicted product of B-myc is a 168-amino-acid protein with extensive homology to the c-Myc amino-terminal region, previously shown to contain a transcriptional activation domain. We hypothesized that B-Myc might also fun...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.13.2.1130
更新日期:1993-02-01 00:00:00
abstract::Saccharomyces cerevisiae contains eight members of a novel and fungus-specific family of bZIP proteins that is defined by four atypical residues on the DNA-binding surface. Two of these proteins, Yap1 and Yap2, are transcriptional activators involved in pleiotropic drug resistance. Although initially described as AP-1...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.17.12.6982
更新日期:1997-12-01 00:00:00
abstract::Approximately half of the introns in Drosophila melanogaster are too small to function in a vertebrate and often lack the pyrimidine tract associated with vertebrate 3' splice sites. Here, we report the splicing and spliceosome assembly properties of two such introns: one with a pyrimidine-poor 3' splice site and one ...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.14.5.3434
更新日期:1994-05-01 00:00:00
abstract::Insulin gene transcription relies on enhancer and promoter elements which are active in pancreatic beta cells. We showed that adenovirus type 5 infection of HIT T-15 cells, a transformed hamster beta cell line, represses insulin gene transcription and mRNA levels. Using expression plasmids transiently introduced into ...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.7.3.1164
更新日期:1987-03-01 00:00:00
abstract::The molecular chaperone HSP90 regulates stability and function of multiple protein kinases. The HSP90-binding drug geldanamycin interferes with this activity and promotes proteasome-dependent degradation of most HSP90 client proteins. Geldanamycin also binds to GRP94, the HSP90 paralog located in the endoplasmic retic...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.22.24.8506-8513.2002
更新日期:2002-12-01 00:00:00
abstract::We have constructed a recombinant pBR322 plasmid composed of a subgenomic transforming fragment of bovine papillomavirus DNA and the hepatitis B surface antigen gene from cloned hepatitis B virus DNA and used it for transfection of NIH 3T3 mouse fibroblasts. The transformed cells retain the plasmids in extrachromosoma...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.3.6.1032
更新日期:1983-06-01 00:00:00
abstract::Using a Saccharomyces cerevisiae strain containing an integrated copy of an H2A-lacZ fusion gene, we screened for mutants which overexpressed beta-galactosidase as a way to identify genes which regulate transcription of the histone genes. Five recessive mutants with this phenotype were shown to contain altered regulat...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.7.12.4204
更新日期:1987-12-01 00:00:00
abstract::Fractalkine (CX(3)CL1) is the first described chemokine that can exist either as a soluble protein or as a membrane-bound molecule. Both forms of fractalkine can mediate adhesion of cells expressing its receptor, CX(3)CR1. This activity, together with its expression on endothelial cells, suggests that fractalkine migh...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/MCB.21.9.3159-3165.2001
更新日期:2001-05-01 00:00:00
abstract::Selective transcription of the insulin gene in pancreatic beta cells is regulated by its enhancer, located within the 5'-flanking region of the insulin gene. Transcription from the enhancer is controlled by both positive- and negative-acting cellular transcription factors. It was previously shown that both the 243- an...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.9.10.4531
更新日期:1989-10-01 00:00:00