A novel N-terminal splice variant of the rat H+-K+-ATPase alpha2 subunit. Cloning, functional expression, and renal adaptive response to chronic hypokalemia.
AuthorsKone BC, Higham SC
JournalJ Biol Chem
PubMed ID9446555
'The H+-K+-ATPase of renal collecting duct mediates K+ conservation during chronic hypokalemia. K+ deprivation promotes H+-K+-ATPase alpha2 (HKalpha2) gene expression in the medullary collecting duct, the principal site of active K+ reabsorption, suggesting that this isozyme contributes to renal K+ reclamation. We report here that alternative transcriptional initiation and mRNA ... More
An alternative processing of integrin alpha(v) subunit in tumor cells by membrane type-1 matrix metalloproteinase.
Authors Ratnikov Boris I; Rozanov Dmitri V; Postnova Tanya I; Baciu Peter G; Zhang Heying; DiScipio Richard G; Chestukhina Galina G; Smith Jeffrey W; Deryugina Elena I; Strongin Alex Y;
JournalJ Biol Chem
PubMed ID11741954
'Membrane type-1 matrix metalloproteinase (MT1-MMP) and alpha(v)beta(3) integrin are both essential to cell invasion. Maturation of integrin pro-alpha(v)chain (pro-alpha(v)) involves its cleavage by proprotein convertases (PC) to form the disulfide-bonded 125-kDa heavy and 25-kDa light alpha chains. Our report presents evidence of an alternative pathway of pro-alpha(v) processing involving MT1-MMP. ... More
Apical sorting of beta-secretase limits amyloid beta-peptide production.
Authors Capell Anja; Meyn Liane; Fluhrer Regina; Teplow David B; Walter Jochen; Haass Christian;
JournalJ Biol Chem
PubMed ID11741885
'Polarized cells such as neurons and endothelial cells appear to be involved in two invariant pathological features of Alzheimer''s disease pathology, namely the formation of senile plaques and cerebral amyloid angiopathy. This implicates polarized sorting mechanisms in the production and accumulation of amyloid beta-peptide (Abeta). We have now studied polarized ... More
Cellular response to oncogenic ras involves induction of the Cdk4 and Cdk6 inhibitor p15(INK4b).
AuthorsMalumbres M, Perez De Castro I, Hernandez MI, Jimenez M, Corral T, Pellicer A
JournalMol Cell Biol
PubMed ID10733595
'The cell cycle inhibitor p15(INK4b) is frequently inactivated by homozygous deletion together with p16(INK4a) and p19(ARF) in some types of tumors. Although the tumor suppressor capability of p15(INK4b) is still questioned, it has been found to be specifically inactivated by hypermethylation in hematopoietic malignancies in the absence of p16(INK4a) alterations. ... More
Insulin-degrading enzyme rapidly removes the beta-amyloid precursor protein intracellular domain (AICD).
'The intramembranous gamma-secretase cleavage of the beta-amyloid precursor protein (APP) is dependent on biologically active presenilins (PS). Notch also undergoes a similar PS-dependent gamma-secretase-like cleavage, resulting in the liberation of the Notch intracellular domain (NICD), which is critically required for developmental signal transduction. gamma-Secretase processing of APP results in the ... More
Overexpression of Fas-ligand by neuroblastoma: a novel mechanism of tumor-cell killing.
'BACKGROUND/PURPOSE: Binding of Fas ligand (Fas-L) to the membrane-bound Fas receptor incites a series of intracellular events that results in programmed cell death or apoptosis. Although this apoptotic phenomenon plays a key role in down-regulating cytotoxic T cells, the authors have shown previously that pancreatic beta cells (bTC) overexpressing Fas-L ... More
Overexpression of Fas ligand does not confer immune privilege to a pancreatic beta tumor cell line (betaTC-3).
'BACKGROUND: Fas ligand (Fas-L) is thought to provide immune privilege to specific tissues and tumors by inducing an apoptotic signal of cytotoxic T cells expressing its Fas receptor. Purpose. The purpose of this work was to evaluate whether an immortalized insulin-secreting cell line (betaTC-3) gains immune privilege by inducing overexpression ... More
Characterization of three alternatively spliced isoforms of the Rel/NF-kappa B transcription factor Relish from the mosquito Aedes aegypti.
Authors Shin Sang Woon; Kokoza Vladimir; Ahmed Abduelaziz; Raikhel Alexander S;
JournalProc Natl Acad Sci U S A
PubMed ID12119421
'The Rel/NF-kappa B transcription factor Relish performs a central role in the acute-phase response to microbial challenge by activating immune antibacterial peptides. We cloned and molecularly characterized the gene homologous to Drosophila Relish from the mosquito Aedes aegypti. Unlike Drosophila Relish, Aedes Relish has three alternatively spliced transcripts encoding different ... More
Matrix GLA protein, a regulatory protein for bone morphogenetic protein-2.
'Matrix GLA protein (MGP) has been identified as a calcification inhibitor in cartilage and vasculature. Part of this effect may be attributed to its influence on osteoinductive activity of bone morphogenetic protein-2 (BMP-2). To detect binding between MGP and BMP-2, we performed immunoprecipitation using MGP and BMP-2 tagged with FLAG ... More
Intracellular localization, function, and dysfunction of the peroxisome-targeting signal type 2 receptor, Pex7p, in mammalian cells.
'We previously isolated and characterized a Chinese hamster ovary (CHO) cell mutant, ZPG207, that is defective in import of proteins carrying a peroxisome-targeting signal type 2 (PTS2) nonapeptide. Herein we have cloned Chinese hamster (Cl) PEX7 encoding the PTS2 receptor. ClPex7p consists of 318 amino acids, shorter than human Pex7p ... More
Missense mutations interfere with VEGFR-3 signalling in primary lymphoedema.
AuthorsKarkkainen MJ, Ferrell RE, Lawrence EC, Kimak MA, Levinson KL, McTigue MA, Alitalo K, Finegold DN
JournalNature Genetics
PubMed ID10835628
Primary lymphoedema is a rare, autosomal dominant disorder that leads to a disabling and disfiguring swelling of the extremities and, when untreated, tends to worsen with time. Here we link primary human lymphoedema to the FLT4 locus, encoding vascular endothelial growth factor receptor-3 (VEGFR-3), in several families. All disease-associated alleles ... More
Protein kinase C regulates the nuclear localization of diacylglycerol kinase-zeta.
AuthorsTopham MK, Bunting M, Zimmerman GA, McIntyre TM, Blackshear PJ, Prescott SM
JournalNature
PubMed ID9716136
Diacylglycerol kinases (DGKs) terminate signalling from diacylglycerol by converting it to phosphatidic acid. Diacylglycerol regulates cell growth and differentiation, and its transient accumulation in the nucleus may be particularly important in this regulation. Here we show that a fraction of DGK-zeta is found in the nucleus, where it regulates the ... More
Growth inhibition by keratinocyte growth factor receptor of human salivary adenocarcinoma cells through induction of differentiation and apoptosis.
Authors Zhang Y; Wang H; Toratani S; Sato J D; Kan M; McKeehan W L; Okamoto T;
JournalProc Natl Acad Sci U S A
PubMed ID11562460
We have reported that normal human salivary gland-derived epithelial cells exclusively express keratinocyte growth factor receptor (KGFR). In the process of malignant transformation of human salivary gland tumors, KGFR gene expression disappeared concomitantly with the de novo expression of the fibroblast growth factor receptor 1 (FGFR1) and FGFR4 genes. In ... More
Mutational study on the roles of disulfide bonds in the beta-subunit of gastric H+,K+-ATPase.
The gastric proton pump, H(+),K(+)-ATPase, consists of the catalytic alpha-subunit and the non-catalytic beta-subunit. Correct assembly between the alpha- and beta-subunits is essential for the functional expression of H(+),K(+)-ATPase. The beta-subunit contains nine conserved cysteine residues; two are in the cytoplasmic domain, one in the transmembrane domain, and six in ... More
Engineered herpes simplex virus 1 is dependent on IL13Ralpha 2 receptor for cell entry and independent of glycoprotein D receptor interaction.
Authors Zhou Guoying; Ye Guo-Jie; Debinski Waldemar; Roizman Bernard;
JournalProc Natl Acad Sci U S A
PubMed ID12417744
In the first stage of engineering a herpes simplex virus (HSV)-1 that specifically targets human malignant glioma cells, we constructed a recombinant virus designated R5111 in which we have ablated the binding sites for sulfated proteoglycans in glycoproteins B and C, replaced the amino-terminal 148 aa in glycoprotein C by ... More
Cyclooxygenase-2 Overexpression Inhibits Platelet-derived Growth Factor-induced Mesangial Cell Proliferation through Induction of the Tumor Suppressor Gene p53 and the Cyclin-dependent Kinase Inhibitors p21waf-1/cip-1 and p27kip-1.
Authors Zahner Gunther; Wolf Gunter; Ayoub Murwan; Reinking Rudiger; Panzer Ulf; Shankland Stuart J.; Stahl Rolf A. K.;
JournalJ Biol Chem
PubMed ID11756433
Cyclooxygenase-2 (COX-2) is an inducible enzyme and serves as a source of paracrine prostaglandin E2 (PGE2) formation in many tissues. In glomerular immune injury COX-2 formation is up-regulated in association with increased mesangial cell growth. To examine whether COX-2 exerts growth modulating effects on glomerular cells, we established two separate ... More
Presenilin-1 mutations of leucine 166 equally affect the generation of the Notch and APP intracellular domains independent of their effect on Abeta 42 production.
The Alzheimer's disease (AD)-associated presenilin (PS) proteins are required for the gamma-secretase cleavages of the beta-amyloid precursor protein and the site 3 (S3) protease cleavage of Notch. These intramembrane cleavages release amyloid-beta peptide (Abeta), including the pathogenic 42-aa variant (Abeta(42)), as well as the beta-amyloid precursor protein and the Notch ... More
The minor subunit splice variants, H2b and H2c, of the human asialoglycoprotein receptor are present with the major subunit H1 in different hetero-oligomeric receptor complexes.
Authors Yik Jasper H N; Saxena Amit; Weigel Paul H;
JournalJ Biol Chem
PubMed ID11943787
The hepatic asialoglycoprotein receptor (ASGP-R) is an endocytic receptor that mediates the internalization of desialylated glycoproteins and their delivery to lysosomes. The human ASGP-R is a hetero-oligomeric complex composed of H1 and H2 subunits. There are three naturally occurring H2 splice variants, designated H2a, H2b, and H2c, although the expression ... More
Regulatory interactions among three members of the vertebrate aryl hydrocarbon receptor family: AHR repressor, AHR1, and AHR2.
The effects of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) and related compounds occur via the aryl hydrocarbon receptor (AHR), a member of the basic helix-loop-helix-Per-ARNT-Sim homology (bHLH-PAS) protein superfamily. A single AHR gene has been identified in mammals, whereas many fish species, including the Atlantic killifish (Fundulus heteroclitus) possess two distinct AHR genes (AHR1 ... More