Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P06889 (Mol)
 630,302 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Somatic cell hybrids were obtained with electric pulse by fusion of human epithelial HeLa cells derived from a carcinoma of the uterine cervix and mouse fibroblasts 3T3.4E, deficient in thymidine kinase. Hybrids were selected and propagated in HAT media; some experiments were carried out in medium with delipidized serum. The hybrid cells were characterized by indirect immunofluorescence with a biotin-streptavidin system using a panel of nine monoclonal antibodies specific for membrane and cytoplasmic antigens of parental cells: intermediate filaments (keratins and vimentin), HLA class 1 (beta 2-microglobulin), cell activation (EGF and transferrin receptors) and cellular adhesion (fibronectin and laminin). All of these antigens were expressed in HeLa cells cultured in conventional medium or with delipidized serum. Conversely mouse fibroblasts contained only vimentin, fibronectin and laminin. All the parental antigens were present in first passage hybrid cells cultured in conventional medium. Vimentin, fibronectin and laminin were maintained in fourth passage hybrids whereas keratins, beta 2-microglobulin, EGF and transferrin receptors were no longer detected. When propagated in medium with delipidized serum, hybrid cells re-expressed these antigens after 5 days of culture. These findings suggest that the reexpression of HeLa cell antigens in hybrid cells was related to deficiency in vitamin A.
Virchows Arch B Cell Pathol Incl Mol Pathol 1989
PMID:Antigenic immunostaining patterns in somatic hybrids of human HeLa cells and mouse fibroblasts 3T3.4E propagated in conventional medium and delipidized serum. 248

Susceptibility to acquire Juvenile Rheumatoid Arthritis (JRA) is linked to HLA-DR5 and DRw8 antigens in Caucasoid populations. However, the frequency of HLA-DR5 is too high in the normal Spanish population and JRA cannot thus be found to be associated with this antigen. It has been found a 14.3 kb-C4-Eco RI restriction fragment length polymorphism which correlates significantly with JRA and may be used as a marker for this disorder in Spaniards.
Mol Immunol 1989 Apr
PMID:An Eco RI polymorphic site in the human complement C4 gene distinguishes juvenile rheumatoid arthritis (JRA) susceptibility-bearing haplotypes. 256 14

The beta 2-adrenergic receptor (ADRB2R) mediates the response of various cel types to neurotransmitters, hormones, and drugs. The platelet-derived growth factor (PDGF) interacts with its receptor (PDGFR) to stimulate mesenchymal cell proliferation. In the human, ADRB2R and PDGFR have been mapped to the q31--q32 region of chromosome 5 (HSA5). Here we report the mapping of Pdgfr and Adrb2r to mouse chromosome 18 (MMU18) using somatic cell hybrid mapping techniques. Together with previous mapping of genes for the glucocorticoid receptor (human locus GRL; mouse locus Gr1-1), the class II HLA invariant chain (human locus PHLAG; mouse locus Ii) and the FMS protooncogene to HSA5 and MMU18, the assignment of both Pdgfr and Adrb2r to MMU18 expands the conserved autosomal syntenic group.
Somat Cell Mol Genet 1989 Jul
PMID:Genes for beta 2-adrenergic receptor and platelet-derived growth factor receptor map to mouse chromosome 18. 256 67

The association of HLA class I and class II antigens, particularly HLA-B8,DR3, with a variety of autoimmune diseases has been well documented. The C4A*Q0 (non-expressed C4A) allele which is in linkage disequilibrium with HLA-B8,DR3 has also been reported to be associated with systemic lupus erythematosus, insulin-dependent diabetes mellitus and Graves' disease. However, the number of studies has been limited by the requirement of family data for the assignment of the C4A*Q0 allele based on C4 protein typing. Recently, with the availability of a C4 cDNA probe, a C4A gene deletion associated with HLA-B8,DR3 has been reported in normal individuals. We have tried to resolve the problem of assigning the C4A*Q0 allele by using both phenotypic and genotypic approaches and have determined the significance of the C4A*Q0 allele in 80 unrelated patients with Graves' disease and in 50 normal control subjects. Our results demonstrate a strong association of the C4A*Q0 allele with Graves' disease (56 versus 26%; P less than 0.002, relative risk = 3.7) and in particular in association with HLA-B8 and/or DR3 (92 versus 70.6%; P less than 0.04) when compared with normal controls. All the C4A*Q0 alleles that were associated with HLA-B8 and/or DR3 were due to a C4A gene deletion. Of the C4A*Q0 alleles, in Graves' disease, 94% (compared with 82% in the control group) could be detected by C4 DNA analysis using either TaqI or EcoRI restriction endonucleases. It is suggested that a combination of C4 protein typing with C4 DNA analysis is the best approach for the determination of the C4A*Q0 allele in unrelated individuals without access to family data.
J Mol Endocrinol 1989 Sep
PMID:C4A gene deletion: association with Graves' disease. 257 May 94

Membranes of human spleen cells were hydrolyzed by papain and the extracellular portions of HLA antigen molecules isolated by monoclonal antibodies fixed on Sepharose. The isolated proteins were spin-labeled by TEMPO-dichlorotriazine. The values of rotational correlation times (tau) of spin-labeled proteins were calculated using dependencies of magnetic parameters found from ESR spectra vs viscosity at constant temperature. The tau-values were equal to 8 nsec for class I molecules and 14 nsec for class II molecules. These values were significantly lower than those predicted for a rigid sphere with dimensions equal to the extracellular portions of HLA molecules (20 nsec). This fact suggests the existence of flexibility in poly-functional HLA molecules, which seems to be important for their biological activity. In this respect, extracellular portions of HLA molecules resemble flexible Fc fragments (tau = 12 nsec) and differ from rigid Fab fragments (tau = 20 nsec) of immunoglobulins G. The rotation of the oligosaccharide chains attached to HLA molecules is restricted.
Mol Immunol 1987 Jul
PMID:Extracellular portions of HLA antigens are not compact globulae. 282 87

The HLA-B7 and HLA-A11 molecules expressed on murine transfectants have been analysed by one- and two-dimensional polyacrylamide gel electrophoresis (PAGE). Two different murine cells, L and P815-HTR have been compared, because it has been previously established that P815 transfectants were much more sensitive to human cytolytic cells than L transfectants. Three kinds of HLA molecules were present on these cells: (1) normal HLA molecules with 2D-PAGE profiles identical to those of the molecules isolated from human cells; (2) HLA molecules of usual size but with more various charges than HLA molecules detected on human cells. This heterogeneity was constantly found with cells expressing HLA-B7 or -A11 antigens, both in L and in P815 transfectants, including several clones. These forms were detected by anti-HLA monoclonal antibodies and by antipeptide (from HLA-B7) antibodies; (3) other unusual products corresponding to shorter heavy chains: molecules of various mol. wts and charges were detected in HLA-B7 but not in HLA-A11 transfectants. They were observed using antipeptide sera but were not seen with anti-HLA monoclonal antibodies. These products were possibly related to the DNA used for transfection and it cannot be excluded that such abnormalities only detectable by antipeptide sera would exist in other transfectants. The functional discrepancies between P815 and L transfectants cannot be clearly explained by these biochemical results.
Mol Immunol 1987 Aug
PMID:Unusual expression of HLA molecules at the surface of murine cells transfected with HLA-B7 or HLA-A11 genes. 282 88

Membranes of human splenocytes were hydrolyzed by papain and extracellular portions of class I and class II HLA antigen molecules were isolated by monoclonal antibodies fixed on Sepharose 4B. The isolated proteins were spin-labeled by TEMPO-dichlorotriazine and the values of rotational correlation times (tau) of labeled proteins were found using dependencies of ESR spectra parameters vs viscosity at constant temperature. The tau-values were equal to 8 ns for class I molecules and 14 ns for class II molecules. These values are 2-3 times lower than predicted for a rigid ellipsoid with mol wt. 50 kDa (about 20 ns). This fact suggests the existence of flexibility of HLA molecules which seems to be important for their biological activity. In this respect extracellular portions of HLA antigen molecules resemble flexible Fc fragments (tau = 12 ns) and differ from rigid Fab fragments (tau = 20 ns) of immunoglobulins G. The values of tau of spin-labeled proteins adsorbed from membrane hydrolysates on IgG-column was equal to 6.5 ns. The proteins adsorbed on lentil lectin column (after isolation of HLA proteins) have the tau-values equal to 9 ns.
Mol Biol (Mosk)
PMID:[Intramolecular mobility of human major histocompatibility complex protein. A spin-label study]. 282 88

Cytotoxic T lymphocytes (CTL) recognize antigen in the context of syngeneic MHC class I gene products. The "learning" of MHC restriction is thought to take place during the early intrathymic development of cytotoxic lymphocyte precursors (CLP). This view does not allow for any significant number of "allorestricted" (as opposed to selfrestricted) T cells to occur among mature, peripheral T cells. Recent evidence indicates, however, that large numbers of antigen-specific, allorestricted CLP can be readily detected among splenic T cell populations from several strains of unprimed normal mice. The frequencies of allorestricted CLP as determined under limiting dilution (LD) culture conditions are in fact in the same order of magnitude as frequencies of selfrestricted CLP. These findings were at the origin of the present study, which was designed to investigate whether antigen-specific, allorestricted CTL populations could also be detected among human peripheral blood T lymphocytes. To address this issue we studied the CTL response to virus-infected allogeneic stimulator cells in two different LD systems. In the first system, peripheral T cells from normal donors were cocultured under precisely defined LD conditions with Epstein-Barr virus (EBV)-transformed allogeneic lymphoblastoid cell lines (LCL). Frequencies of CLP that lysed the stimulating LCL ranged from one in 70 to one in 200, while frequencies of CLP that lysed the respective allogeneic ConA blast targets were 3-40-fold lower. The split-well analysis suggested that a large fraction of developing CTL colonies specifically lysed the stimulating LCL targets but neither the respective ConA blasts nor HLA-mismatched third party LCL targets. CTL generated in this culture system thus displayed allorestricted specificity for LCL membrane antigens. Comparable results were obtained in a second LD system where T cells from normal donors were cocultured with mumps virus-infected allogeneic mononuclear cells (MNC) or ConA blasts. One of 600 to one of 2,800 T cells gave rise to a cytotoxic colony that lysed mumps virus-infected stimulator-derived ConA blast target cells. To assess the lytic specificity of the in vitro expanding CTL populations, individual microcultures were split into three aliquots and tested for cytolytic activity against mumps virus-infected and noninfected specific targets as well as mumps virus-infected, HLA-mismatched third party targets. Clonal CTL populations from four of seven donors lysed virus-infected stimulator targets but did not lyse either noninfected stimulator targets or mumps virus-infected third party targets, i.e., they again showed an antigen-specific allorestricted lytic r
J Mol Cell Immunol 1987
PMID:Human cytotoxic T lymphocytes. III. Large numbers of peripheral blood T cells clonally develop into allorestricted anti-viral cytotoxic T cell populations in vitro. 285 6

Congenital adrenal hyperplasia (CAH) is due to defective adrenal cortisol biosynthesis. In most cases, deficiency of a P 450-C21 specific steroid hydroxylase impairing cortisol synthesis has been found. The disease is HLA-linked, and on clinical grounds it can be divided into two major forms, the classical and the non-classical type. Here, evidence is presented that the classical and the non-classical forms of CAH caused by 21-OH deficiency are due to different genetic alterations in the C4/21-OH gene region. In most cases of classical CAH associated with the HLA-Bw47 antigen, a specific and selective loss of the 21-OH B gene was observed with some interesting exceptions. Alterations in the 21-OH gene region in the non-classical forms of CAH, patients either HLA-B14; DR1 homo- or heterozygous, are different. Our data indicate the possibility of gene conversion events in this genomic region in non-classical CAH.
Mol Biol Med 1986 Oct
PMID:Classical and late-onset forms of congenital adrenal hyperplasia caused by 21-OH deficiency reveal different alterations in the C4/21-OH gene region. 288 4

HLA-DR and -DQ serotyped cell lines and peripheral blood leucocytes were analysed by Southern blot allogenotyping. Using a short DQ beta cDNA probe, a DQ beta allelic series was defined by restriction fragment length polymorphism (RFLP) with the restriction endonuclease TaqI. This DQ beta allelic series correlates with, and defines splits of, the HLA-DQ serological specificities DQw1 (DQ beta 1a and DQ beta 1b RFLPs), DQw2 (DQ beta 2a and DQ beta 2b RFLPs) and DQw3 (DQ beta 3a and DQ beta 3b RFLPs). By sequential use of a short DQ alpha cDNA probe a second, DQ alpha allelic series is defined by RFLP. This series correlates to a lesser extent than DQ beta RFLPs with the HLA-DQ serological specificities. Thus, two DQ alpha RFLPs correlate with a single DQ serotype (DQ alpha 1a and DQ alpha 1c with DQw1), but three DQ alpha RFLPs correlate with more than one DQ serotype (DQ alpha 1b with DQw1 and DQw3; DQ alpha 2 with DQw2 and DQw3; DQ alpha 3 with DQw2 and DQw3). Individual DQ beta and DQ alpha RFLP subtypes appear to correlate with single, or associated HLA-DR specificities. Specific combinations of DQ beta with DQ alpha RFLPs also correlate with HLA-Dw splits of DR2 and DRw6. A system for HLA-DNA typing is described, which uses RFLP patterns generated by sequential hybridization of TaqI-digested DNAs with short DR beta, DQ beta and DQ alpha cDNA probes. The DQ beta and DQ alpha probes not only identify the DQ allele, but because of linkage disequilibrium with DR, help to assign the DR allele, which may not always be identified with a DR beta probe alone.
Mol Immunol 1987 May
PMID:Allogenotypes defined by short DQ alpha and DQ beta cDNA probes correlate with and define splits of HLA-DQ serological specificities. 288 37


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