Biomedical subjects

D A Thompson

Publications and source records attributed to D A Thompson.

At least 73 records · Page 4Linked to original sources

PubMed1998

6-C-kine (SLC), a lymphocyte adhesion-triggering chemokine expressed by high endothelium, is an agonist for the MIP-3beta receptor CCR7.

The beta chemokine known as 6-C-kine, secondary lymphoid-tissue chemokine (SLC), TCA4, or Exodus-2 (herein referred to as 6CK/SLC) can trigger rapid integrin-dependent arrest of lymphocytes rolling under physiological shear and is highly expressed by high endothelial venules, specialized vessels involved in lymphocyte homing from the blood into lymph nodes and Peyer's patches. We show that 6CK/SLC is an agonist for the lymphocyte chemoattractant receptor, CCR7 (EBI-1, BLR-2), previously described as a receptor for the related beta chemokine MIP-3beta (ELC or Exodus-3). Moreover, 6CK/SLC and MIP-3beta attract the same major populations of circulating lymphocytes, including naive and memory T cells > B cells (but not natural killer cells); desensitization to MIP-3beta inhibits lymphocyte chemotaxis to 6CK/SLC but not to the alpha chemokine SDF-1 (stromal cell-derived factor); and 6CK/SLC competes for MIP-3beta binding to resting mouse lymphocytes. The findings suggest that the majority of circulating lymphocytes respond to 6CK/SLC and MIP-3beta in large part through their common receptor CCR7 and that these molecules may be important mediators of physiological lymphocyte recirculation in vivo.

Animals↗

PubMed1998

Characterization of a gene that is inversely correlated with estrogen receptor expression (ICERE-1) in breast carcinomas.

Differential display was used to compare patterns of gene expression in two estrogen receptor (ER)-positive breast carcinoma cell lines (MCF7 and T-47D) and two ER-negative breast carcinoma cell lines (MDA-MB-231 and HBL-100). A 377-bp fragment was identified that was overexpressed in the ER-negative cell lines. Sequence analysis of this clone and comparison with the GenBank/EMBL databases indicated that it did not match any genes published previously. The expression pattern of this gene was inversely correlated with the expression of ER and has been termed ICERE-1 (inversely correlated with estrogen receptor expression). A longer clone of ICERE-1 was isolated from a MDA-MB-231 cDNA library and sequence analysis indicated that this 2168-bp cDNA contained an ORF encoding a protein of 234 amino acids that bears little similarity with any previously described protein sequence. Northern blot analysis of a panel of breast cancer cell lines demonstrated that an ICERE-1 mRNA of approximately 2.2 kb was abundantly expressed in the ER-negative breast carcinoma cell lines, MDA-MB-231 and HBL-100, and the ER-negative cell lines. HEC-1-B, HeLa, and 293. Expression of ICERE-1 was absent or minimal in the ER-positive breast carcinoma cell lines MCF7, T-47D, MDA-MB-361, ZR-75-1, BT-474 and BT-20. Reverse transcription/PCR was used to examine ICERE-1 expression in 29 primary breast carcinomas, 15 of which had been designated as ER positive and 14 as ER negative by immunohistochemistry. The expression level of ICERE-1 was significantly lower (P < 0.001) in the ER-positive tumors compared with the ER-negative tumors. The pattern of expression of ICERE-1 indicates that this gene may be involved in tumor biology specific to hormonally unresponsive breast cancers.

Amino Acid Sequence↗

PubMed1998

Differential screening and suppression subtractive hybridization identified genes differentially expressed in an estrogen receptor-positive breast carcinoma cell line.

Differences in gene expression are likely to explain the phenotypic differences between hormone-responsive and hormone-unresponsive breast cancer. We have identified differentially expressed cDNAs in the estrogen receptor (ER)-positive MCF7 breast carcinoma cell line compared with the ER-negative MDA-MB-231 breast carcinoma cell line. Differential screening isolated four differentially expressed genes: cytokeratin 8, cytokeratin 18, Hsp27 and GPCR -Br. To identify differentially expressed genes of lower abundance, suppression subtractive hybridization was utilized and 29 differentially expressed clones were isolated. Sequence analysis revealed that 11 clones were from previously described genes: HEK8, neuropeptide Y receptor Y1, p21 WAF-1, p55 PIK, cytokeratin 18 (cloned twice), fructose-1,6-biphosphatase, cytokeratin 8, TGFbeta1 binding protein, elongation factor 1alpha2 and pS2. The remaining 18 clones did not match sequences in the GenBank/EMBL database, indicating that they may be novel genes. Expression of pS2, neuropeptide Y receptor Y1 and three novel clones was induced by estradiol, indicating estrogen-responsiveness. The expression pattern of one novel gene, DEME -6, correlated with expression of ER and ERF -1/ AP -2gamma in a panel of breast carcinoma cell lines. A 2.6 kb cDNA of DEME -6 was sequenced and contains an open reading frame of 574 amino acids that demonstrates 62.4% similarity with a gene from Caenorhabditis elegans chromosome III. Expression of DEME -6 was also detected in primary breast carcinomas but not in normal breast tissue, as determined by RT-PCR. These findings support the hypothesis that a set of genes coordinately regulated with ER , but not necessarily estradiol-responsive, are characteristic of the hormone-responsive breast cancer phenotype.

Amino Acid Sequence↗

PubMed1998

Chemokines and the arrest of lymphocytes rolling under flow conditions.

Circulating lymphocytes are recruited from the blood to the tissue by rolling along the endothelium until being stopped by a signaling event linked to the Gialpha subunit of a heterotrimeric GTP-binding protein; that event then triggers rapid integrin-dependent adhesion. Four chemokines are now shown to induce such adhesion to intercellular adhesion molecule-1 and to induce arrest of rolling cells within 1 second under flow conditions similar to those of blood. SDF-1 (also called PBSF), 6-C-kine (also called Exodus-2), and MIP-3beta (also called ELC or Exodus-3) induced adhesion of most circulating lymphocytes, including most CD4+ T cells; and MIP-3alpha (also called LARC or Exodus-1) triggered adhesion of memory, but not naïve, CD4+ T cells. Thus, chemokines can regulate the arrest of lymphocyte subsets under flowing conditions, which may allow them to control lymphocyte-endothelial cell recognition and lymphocyte recruitment in vivo.

Antigens, Surface↗

PubMed1998

Localization of receptors for luteinizing hormone/chorionic gonadotropin in neural retina.

Although the expression of the luteinizing hormone (LH)/human chorionic gonadotropin (CG) receptor gene has been traditionally thought to be restricted to gonadal tissue, recent studies have shown that LH/CG receptors are present in many regions of the central nervous system (CNS), as well as in peripheral tissues. We now report the characterization of LH/CG receptor gene expression in the neural retina, a component of the CNS. Transcript levels in the retina are approximately equal to levels present in the cerebral cortex, but are at least 100 fold lower than the levels in testis. The density of LH/CG receptor transcripts, receptor protein and 125I-CG binding is the highest in the photoreceptor cells and then decreased throughout the inner retina. Our study is the first to demonstrate the presence of LH/CG receptors in the neural retina. This finding raises the possibility that photoreceptor cells have the potential to mount cellular responses to LH/CG that may impact on visual processing, and poses an intriguing connection to the proposed role of gonadotropins in the progression of proliferative retinopathy.

Animals↗

PubMed1998

Novel trabecular meshwork inducible glucocorticoid response mutation in an eight-generation juvenile-onset primary open-angle glaucoma pedigree.

OBJECTIVE: This study aimed to update a large kindred with juvenile-onset primary open-angle glaucoma (POAG) first described in 1940 and to identify the underlying genetic cause of the disease. DESIGN: Molecular genetic study of a single kindred, including clinical examination, retrospective review of clinical and family history records, linkage analysis, and mutation screening. PARTICIPANTS: The retrospective review included 957 members of a single large family. The linkage study included 40 members of 1 branch of the family in which juvenile-onset POAG is segregating in an autosomal-dominant pattern. Mutation screening included 15 at-risk family members with juvenile-onset POAG, probands of 40 families with adult-onset POAG, probands of 11 additional unrelated juvenile-onset POAG families, and 43 unrelated normal control subjects. INTERVENTION: Clinical and family history records were obtained, ophthalmologic examinations were performed, and blood samples were drawn for use in genotyping. MAIN OUTCOME MEASURES: Allele sizes of microsatellite repeat genetic markers from the vicinity of the GLC1A glaucoma gene on chromosome 1q were assigned based on size fractionation of DNA fragments generated by polymerase chain reaction (PCR). Linkage was established by the method of lod scores. Mutations were identified by determination of the DNA sequence of PCR products amplified from the trabecular meshwork inducible glucocorticoid response (TIGR) gene. Glaucoma status for purposes of linkage and mutation analysis was based on a combination of ophthalmologic examination, clinical records, family history, and previously published information. For some individuals reported in the pedigree, but not included in the genotyping studies, less information was available as presented in the text and tables. RESULTS: Autosomal-dominant POAG was confirmed or reported for 78 members of an 8-generation family. Linkage analysis showed significant evidence for linkage of juvenile-onset POAG in one branch of the family to D1S452 (maximum lod score of 6.42 at a recombination fraction of 0.00) and other markers in the vicinity of the GLC1A gene on chromosome 1q. Screening of the TIGR gene identified a mutation that results in substitution of asparagine for isoleucine at codon 477 near the carboxyterminal end of the protein. CONCLUSIONS: The authors' findings strongly suggest that the juvenile-onset POAG locus in this family is the GLC1A locus and that the underlying cause of the disease is the IIe477Asn TIGR mutation that cosegregates with juvenile-onset POAG in one branch of this large family. Lack of samples from deceased individuals prevented the authors from determining whether reported adult-onset cases in this family could also be attributed to the IIe477Asn TIGR mutation. Absence of the IIe477Asn TIGR mutation from other juvenile- and adult-onset POAG families implies that this TIGR mutation is not a common cause of glaucoma.

Adolescent↗

PubMed1998

Expression of bovine activin-A and inhibin-A in recombinant baculovirus-infected Spodoptera frugiperda Sf 21 insect cells.

Currently, bioactive activin and inhibin for investigative purposes are obtained either by purification from bovine or porcine follicular fluid or have been kindly supplied in limited amounts by Genentech. The latter are recombinant formulations produced in cultured monkey kidney CV-1 cells. The aims of this study were to assess the potential of the baculovirus expression system as an alternative means to produce recombinant activin and inhibin. Towards these goals, two recombinant baculoviruses, AcBovACTA and AcBovINHA, were constructed. AcBovACTA contains a contiguous copy of the bovine beta A-inhibin/activin structural gene encoding the beta A-preproprotein whereas AcBovINHA contains contiguous copies of the bovine alpha-inhibin and beta A-inhibin/activin structural genes encoding the alpha- and beta A-preproproteins, respectively. Western blot analyses, using monoclonal antibodies specific for the mature portions of the alpha-inhibin and beta A-inhibin/activin subunits, demonstrated that Spodoptera frugiperda Sf21 cells infected with either recombinant virus secreted mature homodimeric activin-A into the medium. In addition, Sf21 cells infected with the recombinant AcBovINHA virus were found also to produce substantial amounts of the alpha-inhibin precursor protein. However, the mature portion of the latter is not secreted into the medium but is retained within infected cells in an incompletely processed form(s). The recombinant activin-A secreted by Sf21 cells infected with the AcBovACTA virus was shown to possess activin bioactivity when analysed by in vitor bioassay and, therefore, provides an alternative route to mammalian cell expression for the production of recombinant activin-A.

Activins↗

PubMed1998

Predicting patient satisfaction: a study of two emergency departments.

To identify perceptions that predict overall patient (dis)satisfaction with Emergency Department (ED) care, we studied responses to a survey mailed to all discharged patients over a 6-month period (Academic Hospital), and to a telephone interview of a random sample of discharged patients over a 1-year period (Community Hospital). The survey and interview both assessed overall satisfaction, as well as satisfaction with perceived waiting times, information delivery, and expressive quality of physicians, nurses, and staff. Data for 1176 patients (training sample) and 1101 patients (holdout sample) who rated overall satisfaction as either "very good" or "very poor" (Academic Hospital), and for 856 patients (training sample) and 431 patients (holdout sample) who rated overall satisfaction as either "excellent" or "poor" (Community Hospital), were retained for analysis. For both hospitals, nonlinear tree models efficiently achieved overall classification accuracy exceeding 98% in training analysis and 95% in holdout analysis (all p < .0001). The findings suggest that overall patient (dis)satisfaction with care received in the ED is nearly perfectly predictable on the basis of patient-rated expressive qualities of ED staff, particularly physicians and nurses. Interventions designed to reinforce positive (and extinguish negative) expressive health-care provider behaviors may cut the number of extremely dissatisfied patients in half.

Chicago↗

PubMed1998

Early VEP and ERG evidence of visual dysfunction in autosomal recessive osteopetrosis.

Autosomal recessive (AR) osteopetrosis has a rapid course and manifests in the first months of life. Visual loss occurs because of optic nerve compromise, and more rarely retinal dysfunction (which may be a part of a primary neurodegeneration). The only curative treatment currently available is bone marrow transplantation (BMT). It has been suggested that BMT is contraindicated if AR osteopetrosis is associated with a primary neurodegeneration. Visual impairment tends to be irreversible after BMT. The young age of the patients makes reliable, objective tests of visual function especially important. We have reviewed the flash electroretinograms (ERGs) and flash and pattern visual evoked potentials (VEPs) recorded without sedation from 15 patients with AR osteopetrosis, 11 of whom were recorded longitudinally. The most frequent, early indication of visual dysfunction was a delay in the pattern or flash VEP latency. This first affects the pattern reversal VEP to small checks. Importantly this often preceded fundal changes of optic disc pallor, and evidence of optic nerve compression on neuroimaging. Only two patients had ERG evidence of retinal dysfunction affecting both rods and cones. One of these patients had a distinctive fundal appearance, but did not have evidence of associated neuronal degenerative disease. The other patient was lost to follow-up. In the patients reviewed in this study successful BMT and optic nerve decompression did not result in VEP improvement. Fundoscopy, VEP and ERG testing are indicated when the diagnosis of AR osteopetrosis is suspected and provide a useful means of monitoring visual involvement.

Bone Marrow Transplantation↗

PubMed1998

Familial congenital saccade initiation failure and isolated cerebellar vermis hypoplasia.

The underlying lesion in congenital saccade initiation failure (c-SIF) ('congenital ocular motor apraxia', 'Cogan's apraxia') is uncertain. Often no abnormality can be found, yet in others a midline cerebellar abnormality has often been reported. We examined this cerebellar association in a brother and sister. In addition to standard ophthalmological and neurological examinations, both siblings underwent ocular motor testing and neuroradiological investigations including CT and MRI. Both siblings exhibited the typical signs of c-SIF, including headthrusting, synkinetic blinking, missed-nystagmus quick phases, mild developmental delay, and speech difficulties. CT and MRI revealed cerebellar vermis hypoplasia in the brother, but appeared normal in the sister. No other neuroradiological abnormalities were detected. These cases highlight the wide variability in the association of vermis abnormalities with c-SIF, despite the inheritance and similar clinical manifestations. They show that either: (1) the vermis is causal in saccade triggering, but that c-SIF may result from very subtle damage that is beyond MRI resolution in some cases; or (2) that a vermis abnormality per se is not causative but only a marker of another subtle abnormality, either structural or possibly biochemical.

Apraxias↗

PubMed1998

Genetic subtype-independent inhibition of human immunodeficiency virus type 1 replication by CC and CXC chemokines.

We have studied the breadth and potency of the inhibitory actions of the CC chemokines macrophage inhibitory protein 1alpha (MIP-1alpha), MIP-1beta, and RANTES against macrophage-tropic (M-tropic) primary isolates of human immunodeficiency virus type 1 (HIV-1) and of the CXC chemokine stromal cell-derived factor 1alpha against T-cell-tropic (T-tropic) isolates, using mitogen-stimulated primary CD4+ T cells as targets. There was considerable interisolate variation in the sensitivity of HIV-1 to chemokine inhibition, which was especially pronounced for the CC chemokines and M-tropic strains. However, this variation was not obviously dependent on the genetic subtype (A through F) of the virus isolates. Peripheral blood mononuclear cell donor-dependent variation in chemokine inhibition potency was also observed. Among the CC chemokines, the rank order for potency (from most to least potent) was RANTES, MIP-1beta, MIP-1alpha. Some M-tropic isolates, unexpectedly, were much more sensitive to RANTES than to MIP-1beta, whereas other isolates showed sensitivities comparable to those of these two chemokines. Down-regulation of the CCR5 and CXCR4 receptors occurred in cells treated with the cognate chemokines and probably contributes to anti-HIV-1 activity. Thus, for CCR5, the rank order for down-regulation was also RANTES, MIP-1beta, MIP-1alpha.

Anti-HIV Agents↗

PubMed1998

Promoter analysis of RPE65, the gene encoding a 61-kDa retinal pigment epithelium-specific protein.

PURPOSE: To identify the functional promoter region and cis-acting elements that regulate the expression of RPE65, the retinal pigment epithelium (RPE)-specific gene responsible for certain forms of autosomal recessive childhood-onset severe retinal dystrophy. METHODS: A human genomic DNA clone containing the 5'-flanking region of RPE65 was isolated and, 4.0 kb proximal to the transcription start site, was sequenced and analyzed for the presence of transcription factor-binding sites. Promoter activity was assayed by transient transfection of luciferase reporter constructs containing nested deletions of the upstream sequence in the human RPE cell lines ARPE19 and D407, as well as in the SK-Mel-28 and HeLa cell lines. Specific DNA protein-binding sites present in the 340 bp upstream of the transcription start site were identified by DNase I footprint analysis. RESULTS: Sequence analysis places the polymorphic marker, D1S2803, within the RPE65 upstream region and identifies a number of sequences homologous to the gene encoding the cellular retinaldehyde-binding protein. Functional analysis indicates that basal promoter activity is conferred by the sequence from -83 to +39 and is approximately equivalent in all cell lines tested, with no other control elements detected in 3.6 kb of the upstream sequence. At least eight protected regions are identified in DNase I footprint assays, including sequences corresponding to the predicted TATA box, AP-4, and nuclear factor-1 DNA protein-binding sites. CONCLUSIONS: These findings localize the basal promoter activity of RPE65, identify potential cis-acting elements that act as positive regulators of gene expression, and suggest that additional regulatory elements are likely to be involved in restricting gene expression to the retinal pigment epithelium. Identification of promoter elements and genetic markers in the upstream sequence will enable the screening of patients with retinal degeneration for possible mutations that affect RPE65 expression.

Base Sequence↗

PubMed1998

Moesin expression is associated with the estrogen receptor-negative breast cancer phenotype.

BACKGROUND: Estrogen receptor (ER)-positive breast carcinomas possess a less aggressive phenotype than ER-negative breast carcinomas. We hypothesize that a set of genes exists that is expressed only in ER-negative breast carcinomas, which account for the more malignant phenotypic characteristics of these tumors. METHODS: We have used a new technique of polymerase chain reaction select suppression subtractive hybridization to identify genes that are expressed only in ER-negative carcinomas. RESULTS: Seventy-one cDNA clones generated by suppression subtractive hybridization were screened by Northern blot analysis with RNA from ER-positive MCF7 and ER-negative MDA-MB-231 breast carcinoma cell lines. Fifteen clones were differentially expressed in MDA-MB-231 cells. Five of these 15 clones were consistently found to be associated with the ER-negative phenotype in a panel of eight breast carcinoma cell lines. Sequence analysis demonstrated that three of these clones were derived from vimentin and two clones from moesin. Western blot analysis with antihuman moesin antibody confirmed that moesin protein was overexpressed in ER-negative breast carcinoma cell lines but absent from ER-positive breast carcinomas. Moesin mRNA was examined in a panel of 29 primary breast carcinomas with semi-quantitative reverse transcriptase-polymerase chain reaction. Moesin expression was found to be decreased significantly in ER-positive compared with ER-negative tumors (P < .01). CONCLUSIONS: Vimentin and moesin are differentially expressed in association with the ER-negative breast cancer phenotype. Moesin is a membrane/actin filament protein involved in dynamic restructuring of the cell surface and filopodia, a cell structure needed for cell adhesion and motility. Moesin may play a role in the invasiveness and pattern of metastasis characteristic of ER-negative breast cancers.

Blotting, Northern↗

PubMed1998

Neuropeptide Y and the retinal pigment epithelium: receptor subtypes, signaling, and bioelectrical responses.

PURPOSE: To characterize the potential for neuropeptide Y (NPY) signaling in the retinal pigment epithelium (RPE) by identifying the NPY receptor subtypes present, determining the effect of NPY on second-messenger production and membrane conductance, and establishing the neural retina as a site of NPY gene expression. METHODS: Neuropeptide Y receptors present in bovine and human RPE were identified using ribonuclease protection assays and reverse transcriptase-coupled polymerase chain reaction. Assays of cyclic adenosine monophosphate (cAMP) and inositol phosphate production were performed using anion exchange chromatography and RPE cultures labeled with tritiated adenine or myo-inositol, respectively. Open-circuit recordings of transepithelial potential and resistance were performed using intact bovine RPE-choroid preparations. Neuropeptide Y-expressing cells in the retina were identified by staining for beta-galactosidase activity in eyes from mice in which lacZ replaces a portion of the NPY gene. RESULTS: Human RPE contained transcripts encoding Y1, Y2, and Y5 receptors, the predominant subtypes present in the central nervous system. Bovine RPE contained transcripts encoding Y2 receptors but not Y1 receptors. However, cultured cells contained transcripts encoding Y1 and Y2 receptors. Neuropeptide Y signaling in cultured bovine RPE occurred predominately through the Y2 receptor subtype, because nanomolar amounts of NPY and NPY13-36, but not [Leu31,Pro34]NPY, significantly inhibited isoproterenol-induced cAMP accumulation. Apical application of NPY increased the transepithelial potential in RPE-choroid preparations. This response was greatly diminished after basolateral membrane Cl- channels were blocked or changes in intracellular Ca2+ concentration were prevented with a Ca2+ chelator. The NPY gene was expressed in amacrine cells of the inner nuclear and ganglion cell layers of the mouse retina. CONCLUSIONS: The discovery of functionally coupled NPY receptors in the RPE represents the identification of a novel site of expression of this receptor family. The effects of NPY on the electrophysiologic properties of the bovine RPE are consistent with a potential paracrine role in regulating basolateral membrane Ca2+-sensitive Cl- conductance linked to Cl- and fluid transport.

Animals↗

PubMed1997

The human papillomavirus-16 E6 oncoprotein decreases the vigilance of mitotic checkpoints.

The E6 and E7 proteins of the high risk human papillomaviruses (HPVs) are consistently expressed in HPV-positive cervical carcinomas. We investigated the ability of HPV-16 E6 and E7 to disrupt mitotic checkpoints in normal diploid human cells. Acute expression of HPV-16 E6, but not HPV-16 E7, decreased the fidelity of multiple checkpoints controlling entry into and exit from mitosis. After irradiation, nearly 50% of cells containing HPV-16 E6 readily entered mitosis as opposed to less than 10% of control cells. Consistent with this, asynchronous populations of cells expressing HPV-16 E6 had increased cdc2-associated histone H1 kinase activity relative to control populations. In addition, HPV-16 E6 increased sensitivity to chemically-induced S-phase premature mitosis and decreased mitotic spindle assembly checkpoint function relative to control populations. HPV-16 E6 mutants with a reduced ability to target p53 for degradation were unable to abrogate mitotic checkpoints, suggesting a possible mechanism by which HPV-16 E6 disrupts mitotic checkpoints. Expression of a mutant p53 gene yielded an intermediate phenotype relative to HPV-16 E6, generating moderate increases in sensitivity to chemically-induced S-phase PCC and mitotic spindle disruption and a heightened propensity to enter mitosis after irradiation.

CDC2 Protein Kinase↗

PubMed1997

Destabilization of the RB tumor suppressor protein and stabilization of p53 contribute to HPV type 16 E7-induced apoptosis.

Cells that express the human papillomavirus (HPV) type 16 E7 oncoprotein are predisposed to undergo apoptosis. Transgenic mice that have E7 expression targeted to either the retinal photoreceptor cells or the lens cells exhibit signs of apoptosis in cells attempting to undergo differentiation. We established a cell culture system to study this process and have determined the domains of E7 that are required for predisposing cells to undergo apoptosis in response to growth arrest signals. Regions within the core pRB binding site of E7 were necessary but not sufficient for inducing apoptosis. Residues within the adenovirus conserved region 1 homology domain and the consensus casein kinase II phosphorylation site are also important for this effect on cell viability. Our data also demonstrate that the ability of E7 to induce destabilization of pRB and stabilization of p53 coincides with E7-mediated transformation and apoptosis.

Animals↗

PubMed1997

Neuropeptide Y receptor genes mapped in human and mouse: receptors with high affinity for pancreatic polypeptide are not clustered with receptors specific for neuropeptide Y and peptide YY.

Ppyr1, Npy5r, and Npy6r, the genes encoding mouse type 4, type 5, and type 6 members of the neuropeptide Y receptor family, have been mapped by interspecific backcross analysis to conserved linkage groups on mouse Chr 14, Chr 8, and Chr 18, respectively. The human genes, PPYR1 and NPY5R, have been localized to chromosomes 10q and 4q, respectively, by analysis of a panel of rodent-human somatic cell hybrids and yeast artificial chromosomes. These studies complete the mapping of the cloned NPY receptor subtypes in human and mouse and, together with previous studies, establish that the genes encoding receptors with high affinity for pancreatic polypeptide are not clustered with the genes encoding receptors specific for neuropeptide Y and peptide YY. The physical association of these receptor genes correlates with ligand-binding properties, rather than sequence identity, and suggests a complex evolutionary relationship.

Animals↗

PubMed1997

Signal transduction due to HIV-1 envelope interactions with chemokine receptors CXCR4 or CCR5.

Infection with HIV-1 requires expression of CD4 and the chemokine receptors CXCR4 or CCR5 at the target cell surface. Engagement of these receptors by the HIV-1 envelope glycoprotein is essential for membrane fusion, but may additionally activate intracellular signaling pathways. In this study, we demonstrate that chemokines and HIV-1 envelope glycoproteins from both T-tropic and macrophage-tropic strains rapidly induce tyrosine phosphorylation of the protein tyrosine kinase Pyk2. The response requires CXCR4 and CCR5 to be accessible on the cell surface. The results presented here provide the first evidence for activation of an intracellular signaling event that can initiate multiple signaling pathways as a consequence of contact between HIV-1 and chemokine receptors.

CD4 Antigens↗