Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0026764 (multiple myeloma)
 36,148 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The kinetics of incorporation of leucine, galactose and mannose into intracellular and secreted myeloma protein, MOPC 21 IgG(1) and MOPC 46 kappa-type light chain, by cell suspensions of two myeloma plasma-cell tumours, MOPC 21 and MOPC 46, were similar. Radioactive galactose was incorporated to over 90% into galactose residues of intracellular and secreted protein, mannose to over 90% into glucosamine and mannose residues of intracellular protein and to over 90% into glucosamine, mannose and fucose residues of secreted protein, but not into galactose residues. The results show that specific residues in the carbohydrate portion of myeloma proteins can be labelled by specific radioactive monosaccharides, and suggest that fucose residues are added, while myeloma protein is in its final stage of secretion from the plasma cell. The kinetics of incorporation indicate at least three sequential precursor-product relationships between different intracellular forms and the secreted form of myeloma protein.
 ...
PMID:Biosynthesis of the carbohydrate portion of immunoglobulins. Kinetics of synthesis and secretion of [3H] leucine-, [3H] galactose- and [3H] mannose-labelled myeloma protein by two plasma-cell tumours. 409 65

Acquisition of carbohydrates in the disulfide-linked heavy (H) and light (L) chain molecules of murine myeloma (ADJPC5), i.e., HH, HHL, and LHHL, was investigated. That some mannose and glucosamine residues are acquired by immunoglobulin precursor molecules was demonstrated by the detection of glucosamine and mannose in HH, HHL, and LHHL. In contrast, galactose was observed solely in LHHL molecules, which have an identical electrophoretic mobility to the secreted product. Furthermore, as judged from cells incubated with [(3)H]leucine, the more juvenile molecules HH and HHL were predominant in the rough microsome fraction, whereas LHHL was the principal molecular species in the smooth microsome fraction. Findings of this type were not observed in rabbit lymph node cells. Thus, galactose, as well as mannose and glucosamine, were found in the more juvenile molecule known for this species (HL). Moreover, the ratio of HL:LHHL, as judged from cells incubated with [(3)H]leucine, was about the same in rough and smooth microsomes.
 ...
PMID:Synthesis and secretion of gammaglobulin by lymph node cells: the acquisition of carbohydrate residues of immunoglobulin in relation to interchain disulfide bond formation (heavy and light chains-murine myeloma-mannose-glucosamine-galactose). 410 96

1. Peptide maps of Fc fragments or heavy chains of 36 G myeloma proteins and two "heavy chain disease" proteins belonging to the four gamma-chain subgroups revealed very striking similarities between them. However differences in a few peptides were noted. This was most pronounced for the Ge(gamma(2)d) subgroup which lacked three peptides characteristic of the other three subgroups. While Fc fragments from different proteins belonging to the same subgroup appeared very similar, minor differences in addition to those based on currently recognized Gm factors were occasionally noted. 2. Fc fragments from Gm(a+) We(gamma(2)b) proteins had a peptide previously shown to be characteristic of normal Gm(a+) gammaG-globulins. Fc fragments from Gm(a-) molecules belonging to the We(gamma(2)b), Vi(gamma(2)c), or Ne(gamma(2)a) subgroups, whether Gm(b+), Gm(f+), or Gm(-), had the peptide previously identified in Gm(b+f+) normal gammaG-globulin. This "non-a" peptide was absent in peptide maps from Gm(-) molecules of the Ge(gamma(2)d) subgroup which contained instead another peptide with the same electrophoretic mobility but migrating slightly further on chromatography. 3. Both the "a" and "non-a" peptides were pentapeptides having three amino acids in common, and differing in the other two. The "a" peptide contained one residue of lysine, aspartic acid, threonine, leucine, and glutamic acid. The "non-a" peptides prepared from Gm(b+), Gm(f+), and Gm(-) proteins were identical and contained one residue of lysine, threonine, and methionine sulfone, and two residues of glutamic acid. 4. Several possible mechanisms for the origin of these differences, and their possible role in serologic specificity are discussed.
 ...
PMID:Structural studies of human gamma-G-myeloma proteins of different antigenic subgroups and genetic specificities. 416 48

The relationship between Inv phenotype and the amino acid residue at position 191 in kappa-type light polypeptide chains derived from the immunoglobulins of ten normal human sera was investigated. In each case, the amino acid present at position 191 correlated with the Inv phenotype of the individual. Kappa chains of seven Inv (-1,3) homozygotes had valine, while those of three Inv (1,3) heterozygotes had some chains with leucine and some with valine at this position. Genes encoding the Inv (1) and Inv (3) variants appear to be expressed equally in the heterozygous state, since approximately equal amounts of each gene product was recovered from heterozygotes. The correlation between Inv phenotype and the amino acid residue present at position 191 is identical to that previously established for kappa-type Bence-Jones proteins and myeloma protein light chains. These observations support the hypothesis that the valine-leucine interchange is encoded by two allelic forms of a single kappa-chain common region gene.
 ...
PMID:Genetics of immunoglobulin kappa-chains: chemical analysis of normal human light chains of differing Inv types. 418 53

Mouse myeloma cells secreting 19S IgM (immunoglobulin M) (MOPC 104E and TEPC 183) or monomer and polymer IgA (immunoglobulin A) (MOPC 315) were incubated with radioactive leucine and the intracellular and secreted immunoglobulins and immunoglobulin subunits were prepared by preparative sucrose-density-gradient centrifugation. Samples were reduced in the presence or absence of isolated J chain, passed over Sephadex G-25 and then incubated at 37 degrees C for 30min with or without a source of disulphide-interchange enzyme. The extent of reassembly of reduced subunits was then evaluated by electrophoresis in polyacrylamide gels. Provided that J chain and the disulphide-interchange enzyme were supplied, both IgM and IgA could be assembled from their respective subunits, obtained by reductive cleavage of polymeric forms. Under similar conditions, assembly of polymeric forms from intracellular or secreted 7S monomer subunits also occurred. Under these conditions polymerization was total, there being no residue of the monomeric form. Reassembly did not occur in the absence of either J chain or the enzyme. All of the J chain released from IgM by reductive cleavage was incorporated back into the reassembled polymer. The J chain is therefore likely to be an essential structural requirement for polymeric immunoglobulins. A variety of controls ruled out non-specific interactions, and further suggested that the amino acid sequence of polypeptide chains determines the specificity of polymerization. The fact that intracellular IgA and IgM monomer subunits known to be deficient in galactose and fucose can be completely polymerized suggests that the addition of carbohydrate does not control polymerization.
 ...
PMID:Biosynthesis of immunoglobulin A (IgA) and immunoglobulin M (IgM). Requirement for J chain and a disulphide-exchanging enzyme for polymerization. 420 52

Cell suspensions of mouse plasma-cell tumour MOPC 315 secreting predominantly IgA (immunoglobulin A) monomer and dimer were incubated with radioactive leucine, mannose, galactose and fucose for various periods of time. The amounts of secreted and intracellular immunoglobulins were measured by co-precipitation with specific antibody, and the molecular species present were assessed by electrophoresis in polyacrylamide gels. Analysis of the secreted myeloma protein demonstrated that monomer and dimer IgA molecules are identical with respect to carbohydrate composition and rate of secretion. Within the cell, the myeloma protein is almost entirely accounted for by monomer units which either leave the cell as such or are polymerized with the addition of J chain close to the time of secretion. The results support the concept of a stepwise addition of carbohydrate residues to IgA immunoglobulin during the process of secretion. Similar patterns of carbohydrate assembly were found for the monomer or dimer molecules. Mannose residues are added at an early stage, whereas fucose is added close to the time of secretion. Galactose is also added early, but some may also be incorporated at a later stage. Control of IgA polymerization is considered unlikely to reflect regulation at the level of carbohydrate addition, and it is suggested that the critical controlling factor is the J chain.
 ...
PMID:Biosynthesis of immunoglobulin A (IgA). Secretion and addition of carbohydrate to monomer and polymer forms of a mouse myeloma protein. 420 51

Glycopeptides have been isolated from tryptic digests of kappa-type light chains separated from human myeloma proteins obtained from the serum of two patients, Car and Rai. The glycopeptides are derived from the variable region of the chain in both cases, but from different sections. On the basis of homology it is deduced that glycopeptide from Car, kappaI type, is derived from position 25-31 whereas that from Rai, kappaII type, is from position 62-77, their sequences being respectively Ala-Ser-Gln-Asn-Ile-Ser and Phe-Ser-Gly-Ser-Gly-Ser-Gly(Thr,Asp)Phe-Thr-Leu-Asx-Ile-Ser-Arg. The significance of the results is discussed in connexion with the nature of the attachment site of carbohydrate to protein.
 ...
PMID:Glycopeptides from human kappa-chains. 511 28

We have shown previously that immunoglobulin M (IgM) is present within IgM-forming cells mainly in its 7S subunit form (IgMs), whereas only fully assembled IgM pentamers are secreted. There is no spontaneous polymerization of intracellular IgMs in cell lysates, suggesting that the 7S subunits had blocked cysteine residues. This suggestion was explored and confirmed in the present paper. Radioactive IgM (secreted) and IgMs (intracellular) were prepared by sucrose-density-gradient centrifugation after incubation of cells of the IgM-producing mouse myeloma MOPC 104E with [(3)H]leucine. We investigated the susceptibility to reduction of fully assembled mouse IgM and its reconstitution from subunits by analysis by polyacrylamide-gel electrophoresis under dissociating conditions. With increasing concentrations of dithioerythritol, interchain disulphide bonds were cleaved in the following order: inter-IgMs subunit, intra-IgMs subunit H-H, intra-IgMs subunit H-L. Removal of the reducing agent from IgM-reduction mixtures by filtration through Sephadex G-25 caused partial reconstitution of IgM at low protein concentrations (5-100mug/ml) and total reconstitution at higher protein concentrations (300mug/ml or more). Isolated radioactive intracellular IgMs showed no tendency to polymerize unless first treated with a reducing agent; under optimum conditions removal of the reducing agent caused 70% of the subunits to be assembled into IgM. Similar assembly occurred when IgMs was isolated from cells that had been lysed in the presence of an irreversible alkylating reagent (iodoacetamide). The intracellular IgMs cysteine residues responsible for inter-IgMs linkage therefore appear to be reversibly blocked within the cells. Assembly into IgM is thus controlled by removal of this block during secretion.
 ...
PMID:Assembly of immunoglobulin M. Blocked thiol groups of intracellular 7S subunits. 512 12

Incorporation of radioactive fucose into the immunoglobulin G1 myeloma protein secreted by mouse plasma-cell tumour MOPC 21 is stereospecific for the l-isomer. Heavy chains of the secreted form of the myeloma protein carry 90% of the label in fucose residues of their carbohydrate moieties. A small but significant amount of the intracellular immunoglobulin G1 of the mouse plasma-cell tumour MOPC 21 appears to be labelled. Serum in the incubation medium supplies low-molecular-weight diffusible substances necessary to maintain continuous secretion of fucose-labelled myeloma protein beyond 2-3h, and of leucine-labelled myeloma protein beyond 6-8h. In medium containing extensively dialysed serum the secretion of leucine- and fucose-labelled myeloma protein can be restored by the addition of 250mum-d-mannose, 250mum-d-galactose and 250mum-glucosamine. Synthesis and secretion appear to be facilitated in the presence of these sugars, although secretion of myeloma protein devoid of terminal fucose residues is possible for a limited time-period.
 ...
PMID:Biosynthesis of the carbohydrate portion of immunoglobulins. Incorporation of radioactive fucose into immunoglobulin G1 synthesized and secreted by mouse plasma-cell tumour MOPC 21. 515 9

Murine myeloma cells (ADJ-PC-5), incubated in vitro with (3)H-leucine, secrete (3)H-immunoglobulin G as a single molecular species as judged by the migration characteristics of the labeled product on sodium dodecyl sulfateacrylamide gel electrophoresis. However, the fact that some of the interchain disulfide linkages of intracellular immunoglobulins had not been acquired permitted the identification of the following intracellular species: LHHL (identical to immunoglobulin G), HHL, HH, and L (H and L refer to heavy and light polypeptide chains, respectively). Although HH and HHL were readily observed, radioactivity was not detected in the region of the gel where HL would be expected. The time course for the appearance of the intermediates indicates that in these cells the first interchain disulfide bond to be formed occurs between heavy chains. In contrast, the interchain disulfide bonds of immunoglobulins derived from rabbit lymph node cells were acquired in a different order. The principal intracellular species observed were LHHL and HL, whereas HHL and HH were not detectable. These findings indicate that in this species the first interchain disulfide bond to be formed is that between the heavy and light chains of immunoglobulin G.
 ...
PMID:Synthesis and secretion of gamma-globulin by lymph node cells, VIII. Order of synthesis of the interchain disulfide linkages of immunoglobulins. 526 57


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>