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J McClary

Publications and source records attributed to J McClary.

6 recordsLinked to original sources
PubMed1999

RAGE mediates a novel proinflammatory axis: a central cell surface receptor for S100/calgranulin polypeptides.

S100/calgranulin polypeptides are present at sites of inflammation, likely released by inflammatory cells targeted to such loci by a range of environmental cues. We report here that receptor for AGE (RAGE) is a central cell surface receptor for EN-RAGE (extracellular newly identified RAGE-binding protein) and related members of the S100/calgranulin superfamily. Interaction of EN-RAGEs with cellular RAGE on endothelium, mononuclear phagocytes, and lymphocytes triggers cellular activation, with generation of key proinflammatory mediators. Blockade of EN-RAGE/RAGE quenches delayed-type hypersensitivity and inflammatory colitis in murine models by arresting activation of central signaling pathways and expression of inflammatory gene mediators. These data highlight a novel paradigm in inflammation and identify roles for EN-RAGEs and RAGE in chronic cellular activation and tissue injury.

Amino Acid Sequence↗
PubMed1998

The novel estrogen-responsive B-box protein (EBBP) gene is tamoxifen-regulated in cells expressing an estrogen receptor DNA-binding domain mutant.

We have identified a 2.6-kb mRNA whose steady state levels are increased 2- to 4-fold by treatment of human mammary epithelial cells (HMEC) stably expressing an estrogen receptor (ER) transgene with either estrogen (E) or the antiestrogen, 4-hydroxy-tamoxifen (HT). The cDNA corresponding to this mRNA encodes a 564-amino acid protein, named estrogen-responsive B box protein (EBBP), that is a new member of a subfamily within the B box zinc finger protein family, which includes transcription factors (e.g. TIF1), tumor suppressor proteins (e.g. PML), and proteins implicated in development (e.g. ret finger protein, XNF7). The EBBP mRNA is detectable by Northern blot analysis in most tissues, with the exception of liver and peripheral blood lymphocytes, and the gene has been mapped to human chromosome 17p11.2. In contrast to most B box family members, EBBP has a predominantly cytoplasmic localization. Studies of the estrogenic regulation of EBBP expression demonstrated that the E-dependent increase in EBBP mRNA levels in the ER-transfected HMEC is an early, ER-mediated, and cycloheximide-insensitive process. In HMEC stably transfected with an ER mutant containing a deletion in the second zinc finger of the DNA-binding domain, E and HT had different effects on EBBP gene expression; EBBP regulation by E was dramatically reduced while the effects of HT were augmented. These data indicate that HT can modulate EBBP mRNA expression through a mutated ER, which has little activity when bound by E, and suggest that different molecular mechanisms control the E and HT responsiveness of the EBBP gene.

Amino Acid Sequence↗
PubMed1992

Cloning of the gene coding for a human receptor for formyl peptides. Characterization of a promoter region and evidence for polymorphic expression.

Recently we reported that, in HL-60 cells, transcription of the formyl peptide receptor (FPR) gene can be up- and downregulated by agents that induce differentiation of HL-60 cells into neutrophils. To begin studying the mechanisms involved in regulation of FPR gene expression, we cloned two human cDNAs and the gene coding for FPR. The genomic clone (pINF14) contained a 14.5-kb insert. A 2.7-kb EcoRI fragment was obtained from pINF14 that hybridized with an FPR open reading frame probe. The EcoRI fragment was sequenced and found to contain an intronless FPR open reading frame. Sequence alignment of the EcoRI genomic fragment with the FPR cDNA revealed that the first 31 bases of 5' untranslated FPR cDNA were not represented in the genomic fragment. Furthermore, a splicing consensus sequence was present in the genomic fragment at the site of divergence with the cDNA sequence. Restriction mapping and Southern blot analysis identified a 121-bp fragment that contained the sequence corresponding to the first 31 bases of 5' untranslated FPR cDNA. An additional (previously undescribed) 15-bp cDNA sequence in the 5' end of FPR were identified using an anchored polymerase chain reaction. This sequence was also contained in the genomic 121-bp fragment. This 121-bp fragment was located 5.2 kb (intron) upstream of the FPR open reading frame. It contained an unusual TATA box and displayed transcriptional activity in vitro and in vivo. Potential binding sites for AP-1 and glucocorticoid receptor were identified upstream of the putative TATA box.(ABSTRACT TRUNCATED AT 250 WORDS)

Base Sequence↗
PubMed1992

Cloning of a cDNA encoding a receptor related to the formyl peptide receptor of human neutrophils.

We cloned a cDNA (RFP) encoding a receptor (RFP) related (70% overall nucleotide homology) to the formyl peptide receptor of human neutrophils (hFPR). RFP is a seven-transmembrane-domain receptor and its distribution is limited to myeloid cells. Domain sequence comparison with hFPR reveals highly conserved regions and provides clues to putative domains involved in ligand binding and receptor desensitization.

Amino Acid Sequence↗
PubMed1991

Sequencing with the large fragment of DNA polymerase I from Bacillus stearothermophilus.

The large fragment of DNA polymerase I, isolated from Bacillus stearothermophilus, was used for dideoxy sequencing. This heat-stable enzyme permits performing sequencing reactions at high temperature to melt secondary structure and results in uniform band intensities and low background on the autoradiogram. The enzyme can be used in the standard Sanger one-step protocol or in a two-step protocol which separates the labeling reaction from the elongation-termination reaction. The enzyme can be used in double-stranded sequencing. 35S-labeled nucleotides may be used instead of 32P-labeled nucleotides. Both 7-deaza-dGTP and dITP can be used during the reaction in order to minimize band compression on the gel. Results presented here indicate that this enzyme should be a useful tool for sequence determination.

Adenosine Triphosphate↗