Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P02774 (Gc-globulin)
 196 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

All seven pure yolk sac tumors of gonadal and extragonadal origin tested showed a bright positive fluorescence for alpha-fetoprotein in the tumor tissue. A positive reaction was seen in both the tumor cells and the hyaline globules. In all cases, however, the positive fluorescence was distributed in some focal areas of the tumor tissue. Certain tumor cells showed a strong granular intracytoplasmic fluorescence, whereas others showed a weak or a negative fluorescence. The fluorescence-positive tumor cells were located mainly in the areas rich in fluorescence-positive hyaline globules. Besides alpha-fetoprotein, certain plasma proteins--albumin, alpha-1 antitrypsin, and transferrin--were also demonstrated in all five yolk sac tumors tested. The pattern of the distribution of positive fluorescence was basically similar to that of alpha-fetroprotein. Other plasma proteins--orosomucoid, haptoglobin, Gc-globulin, alpha-2 macroglobulin, hemopexin, and ceruloplasmin--were present in certain tumors, and were distributed mainly in a limited number of hyaline globules. Both IgG and IgA were present in two tumors of ovarian origin. The immunoglobulins were for the most part present in extracellular hyaline globules, suggesting that these are taken up from the circulation. Test for fibrinogen, beta-lipoprotein, IgM, IgE, beta-1C/beta-1A and beta-1E globulins were negative or questionable. In a hepatoblastoma, tests for alpha-fetoprotein were positive, but those for other plasma proteins were negative. Fine granular fluorescence was seen in each hepatocellular tumor cell. Mesenchymal elements were virtually unstained.
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PMID:Immunofluorescent demonstration of alpha- fetoprotein and other plasma proteins in yolk sac tumor. 6 8

Vitamin D-binding protein (DBP), a member of a multigene family including alpha-fetoprotein (AFP) and albumin, is a serum glycoprotein that reversibly binds and transports vitamin D and its metabolites to target cells. In this work, we demonstrate that normal and malignant human B-lymphocytes specifically bind and internalize DBP. Radioiodinated DBP (125I-DBP) was used to follow the uptake of the protein by Raji cells, a human pre-B-lymphoma cell line. Time course studies of DBP uptake by these cells exhibited a saturable profile at both 4 and 37 degrees C. The binding saturation curve obtained by incubating Raji cells at 4 degrees C with different concentrations (1.5 nM to 1.5 microM) of 125I-DBP showed two saturation plateaus; Scatchard analysis showed the presence of two groups of receptor sites with a Kd1 of 2.04 x 10(-7) M (n1 = 42,161 +/- 4,336 sites/cell) and a Kd2 of 1.01 x 10(-6) M (n2 = 198,000 +/- 48,000 sites/cell). After incubation of Raji cells at 37 degrees C with both fluorescein isothiocyanate (FITC) and horseradish peroxidase conjugates, DBP was internalized and could be localized in the cytoplasm. DBP-horseradish peroxidase conjugates were used to follow the uptake and to determine the endocytic pathway of the protein in Raji cells. The initial steps, contrary to those observed for AFP, did not apparently involve coated pits and vesicles. Small vesicles (approximately 50-60 nm) with electron-dense DBP-horseradish peroxidase reaction products were observed that could fuse with large endosomes. These endosomes appeared dispersed in the cytoplasm with some preferential localization in the Golgi centrosphere region. Pulse-chase experiments showed that only 10% of the uptaken protein was released in a nondegraded form. Accordingly, most DBP molecules accumulated in endosomes should be degraded in lysosomes, instead of being recycled back to the surface, as in the case of AFP. Contrary to malignant B-cells (Raji), the uptake ability for DBP of normal quiescent B-lymphocytes was very low. Specific binding and internalization of DBP-FITC by these cells were observed following mitogen-induced activation. Significant values of uptake were obtained at 37 degrees C after 72 h of incubation in the presence of pokeweed mitogen. The binding of DBP-FITC was partially inhibited in the presence of an excess of unlabeled protein. Taken together, the actual results suggest that DBP receptors are constitutively expressed by malignant B-cells and in a transitory form by normal B-lymphocytes undergoing mitogen-induced activation.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Receptor-mediated uptake and processing of vitamin D-binding protein in human B-lymphoid cells. 137 1

The vitamin D binding protein (DBP), alternatively known as Gc-globulin, is a member of the albumin (ALB) and alpha-fetoprotein (AFP) gene family. The rat DBP gene is expressed at high levels in liver and at moderate levels in kidney, testis, abdominal fat, and yolk sac. Very low levels of DBP as well as ALB and AFP transcripts can be detected in all other tissues studied by the reverse transcriptase/polymerase chain reaction technique. During development, liver DBP gene transcripts are detectable at 14 days of gestation and levels rise gradually until adulthood in parallel with ALB. DBP present on the surface of U937 monocyte-derived cells is acquired from serum, suggesting cell surface binding sites for DBP. The rat DBP gene has been cloned and characterized. It spans 35 kb and contains 13 exons and 12 introns. The DBP gene contains two fewer exons than the ALB or AFP genes, accounting for the shortest size of its mRNA and protein product. Its 5'-flanking region contains a high degree of structural similarity to both ALB and AFP promoters.
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PMID:Vitamin D binding protein: genomic structure, functional domains, and mRNA expression in tissues. 195 76

A near full-length cDNA encoding the human vitamin D-binding protein (hDBP) was isolated from a human liver mRNA expression library. Complete sequence analysis of this clone predicts the full-length amino acid sequence of the pre-hDBP. Comparison of the sequence of the hDBP mRNA and protein to existing protein and nucleic acid data banks demonstrates a strong and highly characteristic homology of the hDBP with human albumin (hALB) and human alpha-fetoprotein (hAFP). Based upon this structural comparison, we establish that DBP is a member of the ALB and AFP gene family.
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PMID:Serum vitamin D-binding protein is a third member of the albumin and alpha fetoprotein gene family. 241 79

We have grown a human hepatoma cell line, designated as HA22T/VGH, from a 52-yr-old male hepatoma patient since July 1, 1980. This cell line has been subcultured more than 100 passages. The chromosome analysis of HA22T/VGH indicated that the chromosome numbers varied from 70 to 146, with the mode of 73. Methylcellulose soft agar assay showed that approximately 40% of the HA22T/VGH cells formed colonies. The HA22T/VGH produced tumors in nude mice. Histopathological studies of the tumor revealed the arrangement of hepatoma. Detected by the complement fixation method HA22T/VGH cells secreted ceruloplasmin, Factor B, C3, C4, Gc-globulin and alpha 1-acid-glycoprotein. These cells contained the liver associated enzymes: alanine amino transferase, tyrosine amino transferase and gamma-glutamyl transferase. HBsAg and alpha-fetoprotein were not detectable in the HA22T/VGH culture media or cell lysates by the radioimmunoassay.
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PMID:[A new human hepatoma cell line: establishment and characterization]. 629 75

The structure and organization of the human vitamin D-binding protein (DBP) gene has been determined. The gene is composed of 13 exons and 12 intervening sequences. With the help of the polymerase chain reaction (PCR) introns were amplified using exon-specific oligonucleotide primers, and were sequenced after subcloning; the exon/intron borders were determined. The introns 2, 5, 7, 9 and 10 were sequenced completely; the introns 1, 3, 4, 6, 8, 11 and 12 were sequenced in part. We designed intron-specific primers for the amplification of each exon by the PCR-method. This permits the analysis of mutational and function-related sites. By comparison with the genes for human albumin and alpha-fetoprotein the gene for DBP/GC is confirmed as a member of this multigene family. The location of the introns in the coding region of the human DBP-gene is identical with the position of the introns in the rat DBP-gene.
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PMID:Sequence and organization of the human vitamin D-binding protein gene. 750 19

The transporter of vitamin D and its metabolites in blood has received increasing attention in recent years, and is recognized to be a member of a gene family that includes albumin and alpha-fetoprotein. Identical to the group specific component (Gc-globulin) of serum, the protein is a single-chain polypeptide constitutively synthesized in liver that circulates in amounts in far excess of normal vitamin D metabolite concentrations in blood. It plays the major role in the egress of endogenously synthesized vitamin D, from skin and appears to restrain D-sterols from too rapid/excessive cell entry. Along with plasma gelsolin, it comprises the plasma actin-scavenger system that facilitates removal of actin, liberated from lysed cells, by depolymerization and prevention of polymerization. Recently, the protein has been shown to behave as a co-chemotaxin specific for the complement peptide C5a, and its sialic acid-free form has been reported to play a role in macrophage activation. The latter functions strongly implicate its participation in inflammation responses. A unifying hypothesis might also suggest the protein to provide focal D-sterol delivery to cells that are important to the resolution of tissue injuries.
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PMID:Plasma vitamin D-binding protein (Gc-globulin): multiple tasks. 762 13

Plasma/serum proteins of fetal blood samples (N = 88) obtained under ultrasound guidance between the 18th and the 39th week of pregnancy, of blood samples collected from premature infants (N = 19), newborns at term (N = 20) and children of less than 5 years of age (N = 55) were analysed by high-resolution two-dimensional polyacrylamide gel electrophoresis. By comparison with adult 'reference' protein maps, tens of different proteins (and some of their genetic variants) were identified on the electrophoretograms. After the 18th week of gestation, albumin, transferrin, Factor B, glu- and lys-plasminogen, antithrombin III, Gc-globulin, alpha 1-antitrypsin, alpha 2-HS-glycoprotein, several apolipoproteins (apo A-I, A-II, A-IV, C-II, C-III, D, E, J), retinol-binding protein, transthyretin and alpha-fetoprotein could be observed. During intrauterine life, the size of the spots corresponding to alpha-fetoprotein progressively decreased, whereas the protein pattern globally showed an increase in the number and in the size of the spots. These modifications were particularly apparent in the regions of the electrophoretograms restricted to the heavy and light chains of IgG and to alpha 1-antichymotrypsin. In addition, we observed an unidentified fetal polypeptide characterized by an apparent molecular weight (M(r)) of 46 kDa (P46) and a pI of 5.0. P46 was present in all fetuses and all infants of less than 2 years of age.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Plasma/serum protein patterns in human fetuses and infants: a study by high-resolution two-dimensional polyacrylamide gel electrophoresis. 851 49

The effects of phorbol esters (phorbol-12,13-dibutyrate, PDB) on alpha-fetoprotein expression and cell growth were assayed by using fetal hepatocytes in primary culture. PDB acts synergistically with epidermal growth factor (EGF) to specifically decrease alpha-fetoprotein (AFP) mRNA levels, without affecting the expression of other genes of the same family, such as albumin and Vitamin D-binding protein (DBP). This effect is PDB-dose dependent, maximal effects being at 10 ng/ml. The implication of protein kinase C (PKC) in this effect seems clear since bisindolylmaleimide (BIS), a specific PKC inhibitor, completely blocks the PDB effect on AFP expression. Nuclear run-on experiments show that the decrease in AFP mRNA levels is mainly due to an inhibition in the transcription rate of the gene. Determination of PKC activities shows that fetal hepatocytes contain mainly Ca(2+)-independent isoenzymes, which patterns of activation was not modified by EGF plus PDB treatment with respect to PDB treatment. We have found that MAPK and JNK activities, c-jun and c-fos mRNA levels and AP-1 binding activity are notably increased when cells are incubated with both EGF and PDB, PDB does not stimulate growth of fetal hepatocytes, measured either as [3H]-thymidine incorporation into DNA or by cell cycle analysis using flow cytometry. All these results suggest that activation of PKC may affect liver gene expression rather than cell growth in fetal hepatocytes.
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PMID:Phorbol esters down-regulate alpha-fetoprotein gene expression without affecting growth in fetal hepatocytes in primary culture. 956 1

The vitamin D binding protein/Gc-globulin (DBP) gene is a member of a multigene cluster that includes albumin (ALB), alpha-fetoprotein (AFP), and alpha-albumin/afamin (AFM). All four genes have structural and functional similarities and map to the same chromosomal regions in humans (4q11-q13), mice, and rats. An accurate physical map of the region encompassing these genes is a prerequisite for study of their respective transcriptional regulation and identification of potential shared regulatory elements. By refining the physical and meiotic maps of the 4q11-q13 region and creating a local PAC contig, the order and transcriptional orientations of these four genes were determined to be centromere-3'-DBP-5'-5'-ALB-3'-5'-AFP-3'-5'-AFM3'-telomere. The ancestral DBP gene was separated from the ALB gene by >1.5 Mb. This organization and spacing establishes a foundation for ongoing functional studies in this region.
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PMID:Physical and meiotic mapping of the region of human chromosome 4q11-q13 encompassing the vitamin D binding protein DBP/Gc-globulin and albumin multigene cluster. 1040 Sep 26


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