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J Lagercrantz

Publications and source records attributed to J Lagercrantz.

31 records · Page 2Linked to original sources
PubMed1996

Characterization of the murine VEGF-related factor gene.

We describe here the molecular cloning and characterization of the murine homolog of the human vascular endothelial growth factor-related factor (VRF) gene. cDNAs for two alternatively spliced forms of the murine vrf gene have been isolated, the putative translation products of which differ at their carboxyl termini due to a shift in reading frame caused by insertion, or lack thereof, of exon 6, in a similar fashion to human VRF (hVRF). The message lacking exon 6 encodes a protein (mvrf167) with 86% identity and 92% conservation of amino acid residues with hVRF. The protein coding region of the gene spans approximately 5kb of genomic DNA and is composed of 8 exons ranging in size from 36 to 398bp. The genomic structure of murine vrf is highly conserved with the human homolog in relation to position of splice junctions and the presence of contiguous exons 6 and 7. A short polymorphic AC repeat is present in the 3' untranslated region of murine vrf. A major band of approximately 1.3kb was expressed in all adult mouse tissues examined.

Amino Acid Sequence↗
PubMed1996

The gene for human glutaredoxin (GLRX) is localized to human chromosome 5q14.

Glutaredoxin is a small protein (12 kDa) catalyzing glutathione-dependent disulfide oxidoreduction reactions in a coupled system with NADPH, GSH, and glutathione reductase. A cDNA encoding the human glutaredoxin gene (HGMW-approved symbol GLRX) has recently been isolated and cloned from a human fetal spleen cDNA library. The screening of a human genomic library in Charon 4A led to the identification of three genomic clones. Using fluorescence in situ hybridization to metaphase chromosomes with one genomic clone as a probe, the human glutaredoxin gene was localized to chromosomal region 5q14. This localization at chromosome 5 was in agreement with the somatic cell hybrid analysis, using DNA from a human-hamster and a human-mouse hybrid panel and using a human glutaredoxin cDNA as a probe.

Animals↗
PubMed1996

Expression of the VEGF-related factor gene in pre- and postnatal mouse.

We have previously identified a novel gene closely related to the vasoactive endothelial growth factor (VEGF) gene. The human VEGF related factor (VRF) gene was initially isolated using an 11q13 specific cosmid probe (D11S750). Subsequently human VRF was used to isolate the corresponding mouse gene (vrf). Here, we report the spatiotemporal expression pattern of vrf during pre- and postnatal development. Mouse vrf gene expression starts early in fetal development. At day 14 post coitum it is expressed in most cells of the embryo although the heart, spinal cord and the cerebral cortex show significantly higher levels of expression than other tissues. At 17 days post coitum expression is almost exclusively seen in heart, brown fat and spinal cord. This pattern of expression could be consistent with a role of vrf as a growth factor in these tissues.

Animals↗
PubMed1996

Isolation and characterization of a novel gene close to the human phosphoinositide-specific phospholipase C beta 3 gene on chromosomal region 11q13.

We describe the isolation, characterization, and genomic structure of a gene, Phospholipase C beta 3 Neighboring gene (PNG), located on chromosome 11q13. The cDNA was isolated using a cosmid that also contains the phospholipase C beta 3 gene (PLCB3). PNG does not have any marked similarity to other known genes on the DNA level. However, analysis of hybridization to a panel of somatic cell hybrids indicates the existence of related sequences on chromosomes 2, 4, 7, and 22. PNG showed expression of a 1-kb message in multiple tissues. The predicted protein is 199 amino acids. The gene spans approximately 2.5 kb, divided into four exons and three introns. It is located 4.4 kb upstream of PLCB3, with the 5' ends facing each other. The intergenic region has been completely sequenced, revealing separate CpG islands at both ends of this region. The islands are separated by a stretch of 2 kb, characterized by periodic alteration of the GC content. The 5'-flanking region of PNG does not contain TATA or CCAAT, suggesting a housekeeping promoter structure.

Amino Acid Sequence↗
PubMed1996

Chromosomal localization and 5' sequence of the human protein serine/threonine phosphatase 5' gene.

Protein phosphorylation plays a crucial role in the regulation of a wide array of proteins involved in many cellular processes. Protein phosphatase 5 (PP5) is a novel member of the protein serine/threonine phosphatase family. The majority of the cDNA sequence of PP5 has been reported recently. In our study, a sequence encoding the whole open reading frame of PP5 was cloned from a human fetal brain cDNA library. The protein phosphatase cDNA sequence of our clone is longer at the 5' end than the recently published sequence. It's likely that the extended sequence contains the start codon ATG, since a translation stop codon TAG is present upstream of the ATG codon in the same open reading frame. The mRNA of the PP5 gene was detected in all the human tissues examined. The PP5 gene was localized to human chromosomal region 19q13.3.

Amino Acid Sequence↗
PubMed1996

Nucleotide sequence of a cDNA clone (SUBT1) partly homologous to a human subtelomeric repeat sequence.

Telomeres contains short tandem repeats (TTAGGG)n that are usually several kilobases in size. DNA sequences located next to the repeats are called telomere-associated or subtelomeric sequences. In this report we describe isolation and characterization of a new cDNA sequence isolated with a telomere specific, chromosome 17 genomic clone. No open reading frame of notable length could be detected. However comparison with sequences in the EMBL/Genbank revealed a 897 bp of close to perfect match, in the 3'end with the centromeric end of a genomic clone containing subtelomeric repeat sequences. The potential function of the SUBT1 transcript remains to be elucidated.

Chromosomes, Human, Pair 17↗
PubMed1996

Cloning and characterization of a novel human gene related to vascular endothelial growth factor.

This paper describes the cloning and characterization of a new member of the vascular endothelial growth factor (VEGF) gene family, which we have designated VRF for VEGF-related-factor. Sequencing of cDNAs from a human fetal brain library and RT-PCR products from normal and tumor tissue cDNA pools indicate two alternatively spliced messages with open reading frames of 621 and 564 bp, respectively. The predicted proteins differ at their carboxyl ends resulting from a shift in the open reading frame. Both isoforms show strong homology to VEGF at their amino termini, but only the shorter isoform maintains homology to VEGF at its carboxyl terminus and conserves all 16 cysteine residues of VEGF165. Similarity comparisons of this isoform revealed overall protein identity of 48% and conservative substitution of 69% with VEGF189. VRF is predicted to contain a signal peptide, suggesting that it may be a secreted factor. The VRF gene maps to the D11S750 locus at chromosome band 11q13, and the protein coding region, spanning approximately 5 kb, is comprised of 8 exons that range in size from 36 to 431 bp. Exons 6 and 7 are contiguous and the two isoforms of VRF arise through alternate splicing of exon 6. VRF appears to be ubiquitously expressed as two transcripts of 2.0 and 5.5 kb; the level of expression is similar among normal and malignant tissues.

Amino Acid Sequence↗
PubMed1995

Expression of the phosphoinositide-specific phospholipase Cbeta3 gene in the rat.

Phospholipase Cbeta3 (PLCbeta3) is a member of the family of phospholipase C isoenzymes, a second messenger system that plays an important role in initiating receptor-mediated signal transduction in response to extracellular signals. Using RNA in situ hybridization we showed that in the embryonic rat nervous system, PLCbeta3 is expressed in dorsal root ganglia (DRGs) and the trigeminal ganglion. Characterization of the hybridization signal in the adult rat nervous system revealed that PLCbeta3 expression is confined mainly to small-sized DRG neurons. In non-neuronal tissues, PLCbeta3 is expressed by cells of epithelial origin, such as skin and the mucous lining airways and the gastrointestinal canal, and in lung and thymus.

Animals↗
PubMed1995

Genomic organization and complete cDNA sequence of the human phosphoinositide-specific phospholipase C beta 3 gene (PLCB3).

We have characterized the complete cDNA sequence, genomic structure, and expression of the human phosphoinositide-specific phospholipase C beta 3 (PLC beta 3) gene (gene symbol PLCB3). PLC beta 3 plays an important role in initiating receptor-mediated signal transduction. Activation of PLC takes place in many cells as a response to stimulation by hormones, growth factors, neurotransmitters, and other ligands. The partial cDNA sequence of PLC beta 3, previously published, was extended with 876 bp in the 5' direction, giving a transcript of 4400 bp and a total open reading frame of 1234 amino acids. This was in accordance with expression analysis by Northern blotting that revealed a single 4.4-kb transcript in all tissues tested. Genomic data were obtained by sequencing plasmid subclones of a cosmid that contained the whole gene. The size of the complete transcription unit was estimated to be on the order of 15 kb. The gene contains 31 exons, with all splice donor and acceptor sites conforming to the GT/AG rule. No exon exceeds 571 bp in length, and the shortest exon spans only 36 bp. More than half of the introns are smaller than 200 bp, with the smallest being only 79 bp long. The transcription initiation site was determined to be within an 8-bp cluster 328-321 bp upstream of the translation initiation site. The 5'flanking region is highly GC rich, with multiple CpG doublets, and contains multiple binding sites for Sp1. Lacking typical transcriptional regulatory sequences such as TATA and CAAT boxes, the putative promoter region conforms to the group of housekeeping promoters.

Amino Acid Sequence↗
PubMed1995

Candidate genes for multiple endocrine neoplasia type 1.

The aim of this study was to isolate and characterize candidates for the multiple endocrine neoplasia type 1 (MEN1) gene. The development of tumours related to MEN1 is associated with somatic deletions involving the MEN1 locus, suggesting inactivation of a tumour-suppressor gene in this region. We have isolated five cDNA candidates located within the 900 kb remaining for the MEN1 gene, determined their sequence, and characterized their expression in normal tissues and several endocrine tumours. One of the candidates, encoding for phospholipase C-beta 3, showed properties consistent with the idea of a tumour-suppressor gene.

Blotting, Northern↗
PubMed1991

Acetone-regulated synthesis and degradation of cytochrome P450E1 and cytochrome P4502B1 in rat liver [corrected].

The regulation of CYP2E1 and 2B1 was studied by following mRNA levels, catalytic activities and the subcellular distribution of the apoproteins in rat liver 0, 6, 12, 24, 48 and 96 h after a single intragastric dose of acetone. No changes were observed in hepatic CYP2E1 mRNA levels at any time after acetone treatment, whereas rapid rises were observed in the microsomal amount of CYP2E1 protein and CYP2E1-catalyzed 4-nitrophenol hydroxylase and carbon-tetrachloride-initiated lipid-peroxidation activities. However, CYP2E1-dependent catalytic activities declined much faster than the immunodetectable CYP2E1 protein, suggesting that this cytochrome P-450 is inactivated prior to degradation. Similar results were seen in primary hepatocyte cultures. By contrast, concomitant changes in levels of CYP2B1 and CYP2B1-dependent O-depentylation of pentoxyresorufin were observed in the same microsomal preparations. Investigation of the degradative mechanism of both CYP2E1 and CYP2B1 by immunoquantitation of the proteins in lysosomes and by immunohistochemistry indicated their degradation via an autophagic-lysosomal pathway. The data suggest that CYP2E1 is acutely inactivated in the endoplasmic reticulum and that degradation of this isozyme occurs, at least in part, by the lysosomal route. By contrast, CYP2B1 is principally controlled at the level of synthesis.

Acetone↗