Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:3.4.24.11 (CD10)
 9,792 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The Kell blood group is a major antigenic system in human erythrocytes. Kell antigens reside on a 93-kDa membrane glycoprotein that is surface-exposed and associated with the underlying cytoskeleton. We isolated tryptic peptides and, based on the amino acid sequence of one of the peptides and by using the PCR, prepared a specific oligonucleotide to screen a lambda gt10 human bone-marrow cDNA library. Four clones were isolated, one containing cDNA with an open reading frame for an 83-kDa protein. All known Kell amino acid sequences were present in the deduced sequence; moreover, rabbit antibody to a 30-amino acid peptide, prepared from this sequence, reacted on an immunoblot with authentic Kell protein. The Kell cDNA sequence predicts a 732-amino acid protein. Hydropathy analysis indicates a single membrane-spanning region, suggesting that Kell protein is oriented with 47 of its N-terminal amino acids in the cell cytoplasm, and a 665-amino acid segment, which contains six possible N-glycosylation sites, is located extracellularly. Computer-based search showed that Kell has structural and sequence homology to a family of zinc metalloglycoproteins with neutral endopeptidase activity.
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PMID:Molecular cloning and primary structure of Kell blood group protein. 171 90

The relationship between growth and cytodifferentiation was studied in cultured human mammary myoepithelial cells under serum-free culture conditions. Myoepithelial-cell differentiation was monitored by quantifying cells showing immunoreactivity to the muscle isoform of actin; to the membrane glycoprotein common acute lymphoblastic leukemia antigen (CALLA); and to type IV collagen. Growth was quantified either by measuring the actual increase in cell number, or in a more-sensitive assay using immunoreactivity to the cell-proliferation-associated nuclear antigen Ki-67 as a measurement of the number of cells leaving the G0-phase of the cell cycle. The results showed that: (a) Primary cultures of myoepithelial cells on DME-F12 supplemented with cholera toxin (CT) alone resulted in the formation of quiescent cell islets (in the G0-phase of the cell cycle) showing phenotypic traits preserved from the in vivo situation (actin- and CALLA-positive cells with little or no type-IV-collagen immunoreactivity). (b) After addition of epidermal growth factor (EGF), with an ED50 of 1-10 ng/ml, in the presence of CT, the cells entered the G1-phase of the cell cycle, without further increase in cell number. At the same ED50 of EGF, the frequency of CALLA-positive cells decreased, while the number of cells immunoreactive for type IV collagen increased with a maximal effect of EGF seen after 7-11 days. During the same period, the cells remained fully differentiated with respect to actin immunoreactivity. (c) Further addition of insulin (I) to the medium in the presence of EGF and CT resulted in the cells entering an exponential growth phase associated with simultaneous decrease in actin immunoreactivity with a maximal effect of I after 11 days of exposure. The dose-response curve to I was virtually identical for stimulating cell proliferation and for reducing the frequency of actin-immunoreactive cells (ED50 in the range of 30 ng/ml), suggesting that the two processes were controlled by the same initial I-receptor interaction. (d) Some reduction in the number of actin-positive cells was exerted by I-EGF-CT independently of the mitogenic response, but this reduction was further augmented if the cells were allowed to proliferate. (e) Time-course studies of quiescent (G0-phase) cells stimulated to exponential growth revealed that entrance of cells into the G1-phase of the cell cycle preceded the loss of muscle actin filaments. (f) Exponentially growing actin-negative epithelial cells did not resume a myoepithelial phenotype in density-arrested postconfluent cultures.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Growth factor control of myoepithelial-cell differentiation in cultures of human mammary gland. 246 50

The common acute lymphoblastic leukemia antigen (CALLA/CD10) is a nonintegral membrane glycoprotein expressed on normal and neoplastic cells of hematopoietic and nonhematopoietic origin. We have undertaken a series of experiments to examine 1) the structural homology between leukemia cell and neutrophil CALLA/CD10 and 2) the putative function CALLA/CD10 subserves to human neutrophils. Biosynthetic labeling, peptide mapping, and two-dimensional gel electrophoresis indicate that neutrophils synthesize and express a CALLA/CD10 molecule that is similar, but not identical, to leukemic cell CALLA/CD10. The level of CALLA/CD10 expression is similar on the two cell populations, and neutrophil CALLA/CD10 (like its leukemic cell counterpart) undergoes antigenic modulation. Finally, we report that neutrophil cell surface-bound anti-CALLA/CD10 monoclonal antibodies inhibit the chemotactic response to both N-Formyl-methionyl-leucyl-phenylalanine (F-mlp) and zymosan-activated sera (ZAS), but had no inhibitory effect on random migration, degranulation, or aggregation. The anti-class I monoclonal antibody W6/32 exerted a similar effect on chemotaxis. We conclude that CALLA/CD10 has no clearly defined role in neutrophil function but may play a role in some distal event in chemotaxis.
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PMID:Structure/function studies of the common acute lymphoblastic leukemia antigen (CALLA/CD10) expressed on human neutrophils. 294 84

Immunohistochemical localization of human leukocyte common antigen (LCA), a major membrane glycoprotein restricted to leukocytes, was evaluated in paraffin sections of a wide variety of hematopoietic and nonhematopoietic tissues (294 specimens) with monoclonal antibodies (PD7/26 and 2B11). In nonneoplastic tissues, LCA was identified on B and T lymphocytes, with variable immunoreactivities for plasma cells and histiocytes. By light microscopy and ultrastructurally, LCA was localized predominantly to the cell membrane and was also present focally in the cytoplasm. Myeloid cells at all stages of maturation were non-reactive, as were erythroid cells, megakaryocytes, and all non-hematopoietic tissues. Monocytes and mast cells, however, revealed membrane staining for LCA. In nearly all non-Hodgkin's lymphomas of the B- and T-cell types (74 of 80; 93 per cent), the lymphoid infiltrate was immunoreactive for LCA. In specimens from patients with Hodgkin's disease (nodular sclerosis and mixed cellularity type), rare Reed-Sternberg cells stained for LCA. Neoplastic cells were consistently immunoreactive for LCA in specimens from patients with chronic lymphocytic leukemia of the B- or T-cell type, prolymphocyte leukemia, and hairy cell leukemia. However, tissues from only three of eight cases of acute lymphoblastic leukemia were LCA-positive, with most non-reactive specimens exhibiting CALLA (J5) positivity. In cases of multiple myeloma, only minor populations of plasmacytic cells exhibited membrane staining for LCA. Nonhematopoietic neoplasms (102 evaluated), including small cell anaplastic carcinomas, amelanotic melanomas, alveolar rhabdomyosarcomas, Ewing's sarcoma, and germ cell tumors, were uniformly non-reactive. Human LCA represents an excellent cell marker for paraffin sections, to distinguish hematopoietic neoplasms, particularly of the lymphoid type, from poorly differentiated tumors of epithelial, mesenchymal, or neural derivation.
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PMID:Leukocyte common antigen--a diagnostic discriminant between hematopoietic and nonhematopoietic neoplasms in paraffin sections using monoclonal antibodies: correlation with immunologic studies and ultrastructural localization. 315 3

It was previously shown that estrogen induces a membrane glycoprotein (molecular mass, 95 kDa) in the chicken oviducts, which exhibits several properties similar to transferrin receptors (Poola, I., and Lucas, J. J. (1988) J. Biol. Chem. 263, 19137-19146). In the present study, we have further investigated its molecular and transferrin binding properties. We have sequenced several internal peptides isolated from the purified protein by endopeptidase Lys-C. We have found that it has a high degree of sequence homologies with those of chicken heat-shock protein (cHsp108), mouse endoplasmic reticulum protein (mERp99), hamster glucose-regulated protein (hagrp94), and human tumor rejection antigen (hTRAgp96), all of which are shown to be highly homologous to each other and to yeast hsp90. We demonstrate here that the [35S]methionine-labeled immunoaffinity-purified estrogen-inducible membrane glycoprotein binds to the transferrin affinity columns similar to iron-modulated transferrin receptors. Indirect immunofluorescence microscopic studies indicate that it is an intracellular glycoprotein unlike transferrin receptors. We have isolated two molecular forms of the protein, with molecular masses of 116 and 104 kDa, by immunoaffinity column purification, immunoprecipitation, Western blotting, and pulse-chase labeling analyses. Both 116-and 104-kDa species bind transferrin. This protein can be induced by heat-shocking the oviduct cells at 45 degrees C for 3h and recovering at 37 degrees C for 2-3 h. It is also expressed in the human breast cancer cell lines, MCF-7 and T-47D. All these properties taken together strongly suggest that the estrogen-inducible membrane glycoprotein is a novel transferrin-binding protein, structurally related to the stress-regulated proteins.
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PMID:The estrogen-inducible transferrin receptor-like membrane glycoprotein is related to stress-regulated proteins. 806 20

The Kell blood group system is complex containing over 20 different antigens. Some of the Kell antigens may be organized in 5 sets of paired alleles with opposing high and low incidence antigens while others are independently expressed. Molecular cloning established that Kell antigens are carried on a 93kDa, type II, membrane glycoprotein. The Kell gene (KEL) is located at 7q 32-36 and spans about 21,5 kb. The coding sequence is organized in 19 exons. The promoter region does not contain TATA sequences but has possible transcription binding sites for GATA-1 and Sp1. Kell protein shares a putative enzymatic active amino acid sequence with a large family of zinc endopeptidases and has closest structural and sequence homology with neutral endopeptidase 24,11 (a.k.a. enkephalinase, CALLA) and endothelin converting enzyme (ECE-1). The molecular basis of several important Kell antigens has been determined and all are due to base substitutions causing single amino acid changes. The K1/K2 polymorphism is due to a C to T substitution in exon 6, encoding a threonine to methionine change. This mutation disrupts an N-glycosylation site. Two PCR-based methods, including use of allele-specific primers, have been developed which may be used to determine fetal K1/K2 genotypes. These tests can potentially identify those pregnancies at risk for hemolytic disease of the newborn. The allelic relationship of Kpa, Kpb and Kpc was confirmed, since single base substitutions in the same codon encode 3 different amino acids.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:The Kell blood group system. 854 22

Mutations in the PEX gene are responsible for X-linked hypophosphatemic rickets. To gain insight into the role of PEX in normal physiology we have cloned the human full-length cDNA and studied its tissue expression, subcellular localization, and peptidase activity. We show that the cDNA encodes a 749-amino acid protein structurally related to a family of neutral endopeptidases that include neprilysin as prototype. By Northern blot analysis, the size of the full-length PEX transcript is 6.5 kilobases. PEX expression, as determined by semi-quantitative polymerase chain reaction, is high in bone and in tumor tissue associated with the paraneoplastic syndrome of renal phosphate wasting. PEX is glycosylated in the presence of canine microsomal membranes and partitions exclusively in the detergent phase from Triton X-114 extractions of transiently transfected COS cells. Immunofluorescence studies in A293 cells expressing PEX tagged with a c-myc epitope show a predominant cell-surface location for the protein with its COOH-terminal domain in the extracellular compartment, substantiating the assumption that PEX, like other members of the neutral endopeptidase family, is a type II integral membrane glycoprotein. Cell membranes from cultured COS cells transiently expressing PEX efficiently degrade exogenously added parathyroid hormone-derived peptides, demonstrating for the first time that recombinant PEX can function as an endopeptidase. PEX peptidase activity may provide a convenient target for pharmacological intervention in states of altered phosphate homeostasis and in metabolic bone diseases.
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PMID:Cloning of human PEX cDNA. Expression, subcellular localization, and endopeptidase activity. 959 14

A disulfide bond links Kell and XK red cell membrane proteins. Kell, a type II membrane glycoprotein, carries over 20 blood group antigens, and XK, which spans the membrane 10 times, is lacking in rare individuals with the McLeod syndrome. Kell is classified in the neprilysin family of zinc endopeptidases, and XK has structural features that suggest it is a transport protein. Kell has 15 extracellular cysteines, and XK has one in its fifth extracellular loop. Five of the extracellular cysteine residues in Kell are not conserved in the other members of the neprilysin family, and based on the hypothesis that one of the nonconserved cysteines is linked to XK, cysteines 72 and 319 were mutated to serine. The single extracellular cysteine 347 of XK was also mutated. Co-expression of combinations of wild-type and mutant proteins in transfected COS-1 cells showed that Kell C72S did not form a Kell-XK complex with wild-type XK, while wild-type Kell and Kell C319S did. XK C347S was also unable to form a complex with wild-type Kell, indicating that Kell cysteine 72 is linked to XK cysteine 347. Kell C72S was transported to the cell surface, indicating that linkage to XK is not required. In addition, chemical cross-linking of red cell membranes with dithiobispropionimidate indicated that glyceraldehyde-3-phosphate dehydrogenase is a near neighbor of Kell.
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PMID:Association of XK and Kell blood group proteins. 959 44

Dipeptidylpeptidase IV (DPP IV, CD26), a serine-type exo- and endopeptidase found in the cell surface membrane of many tissues, was employed as a model membrane glycoprotein to study the expression of sialoforms on cell surface glycoproteins. Native, enzymatically active DPP IV was purified from plasma membranes of kidney and liver by lectin affinity chromatography in conjunction with crown ether anion exchange chromatography. The enzyme was gradient-eluted in continuous fractions, all showing a single polypeptide band of about 100 kDa when separated by sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) under reducing, denaturing conditions. Analysis of the purified DPP IV by isoelectric focusing (IEF) showed that it consists of several polypeptides of different isoelectric points (IP) ranging from 5.5 to 7.0. In vitro- desialylation of the enzyme and subsequent isoelectric focusing revealed that the differences in isoelectric points were due to differences in the degree of sialylation. Differences in the degree of sialylation between the fractions were also demonstrated by SDS-PAGE under nonreducing and nondenaturing conditions. Increased sialylation of the enzyme as demonstrated by isoelectric focusing resulted in increased migration velocity in nonreducing and nondenaturing SDS-polyacrylamide gels. In vitro -desialylation of the enzyme and its resialylation confirmed that sialylation was responsible for this extraordinary migration behavior. The native enzyme was predominantly sialylated via alpha 2, 6-linkage, as shown by lectin affinity blotting employing Sambucus nigra agglutinin (SNA) and Maackia amurensis agglutinin (MAA). These findings demonstrate that a distinct membrane glycoprotein may exist in various sialoforms, distinguished from each other by a different number of sialic acid residues. Moreover, these sialoforms can be individually purified by crown ether anion exchange chromatography.
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PMID:Sialoforms of dipeptidylpeptidase IV from rat kidney and liver. 1056 54

Expression of the Kell blood group system is dependent on two proteins, Kell and XK, that are linked by a single disulfide bond. Kell, a type II membrane glycoprotein, is a zinc endopeptidase, while XK, which has 10 transmembrane domains, is a putative membrane transporter. A rare phenotype termed Kell null (Ko) is characterized by the absence of Kell protein and Kell antigens from the red cell membrane and diminished amounts of XK protein. We determined the molecular basis of eight unrelated persons with Ko phenotypes by sequencing the coding and the intron-exon splice regions of KEL and, in some cases, analysis of mRNA transcripts and expression of mutants on the cell surface of transfected cells. Six subjects were homozygous: four with premature stop codons, one with a 5' splice site mutation, G to A, in intron 3, and one with an amino acid substitution (S676N) in exon 18. Two Ko persons with premature stop codons had identical mutations in exon 4 (R128Stop), another had a different mutation in exon 4 (C83Stop), and the fourth had a stop codon in exon 9 (Q348Stop). Two Ko persons were heterozygous for two mutations. One had a 5' splice site mutation (G to A) in intron 3 of one allele that caused aberrant splicing and exon skipping, and the other allele had an amino acid substitution in exon 10 (S363N). The other heterozygote had the same amino acid substitution in exon 10 (S363N) in one allele and a premature stop codon in exon 6 (R192Stop) in the other allele. The S363N and S676N mutants, expressed in 293T cells, were retained in a pre-Golgi compartment and were not transported to the cell surface, indicating that these mutations inhibit trafficking. We conclude that several different molecular defects cause the Kell null phenotype.
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PMID:Molecular defects underlying the Kell null phenotype. 1137 1


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