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

The proteins programmed in the wheat-germ cell-free system by the mRNA coding for the MOPC-321 mouse myeloma L (light) chain were labelled with [35S]methionine, [4,5-3H]leucine or [3-3H]serine, and were subjected to amino acid-sequence analyses. Over 95% of the total cell-free product was sequenced as one homogeneous protein, which corresponds to the precursor of the L-chain protein. In the precursor, 20 amino acid residues precede the N-terminus of the mature protein. This extra piece contains one methionine residue at the N-terminus, one serine residue at position 18, and six leucine residues, which are clustered in two triplets at positions 6, 7, 8 and 11, 12, 13. The identification of methionine at the N-terminus of the precursor is in agreement with the evidence showing that unblocked methionine is the initiator residue for protein synthesis in eukaryotes. The absence of methionine at position 20, which precedes the N-terminal residue of the mature protein, suggests that myeloma cells synthesize the precursor. However, within the cell the precursor should be rapidly processed to the mature L chain, since precursor molecules have not yet been found in the intact animal. The abundance (30%) of leucine residues indicates that the extra-piece moiety is quite hydrophobic. The extra piece of the MOPC-321 L-chain precursor synthesized with the aid of the Krebs II ascites cell-free system is of identical size and it has the same leucine sequence [Schechter et al. (1975) Science 188, 160-162]. This indicates that cell-free systems derived from the plant and animal kingdom initiate mRNA translation from the same point. It is shown that the amino acid sequence of minute amounts of a highly labelled protein (0.1 pmol) can be faithfully determined in the presence of a large excess (over 2000 000-fold) of unrelated non-radioactive proteins.
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PMID:Identification of N-terminal methionine in the precursor of immunoglobulin light chain. Initiation of translation of messenger ribonucleic acid in plants and animals. 82 67

The proteins programmed in the wheat-germ cell-free system by the mRNA coding for the MOPC-63 mouse myeloma L (light) chain were labelled with six radioactive amino acids: [35S]methionine, [4,5-3H]leucine, [3,4-3H]proline, [3-3H]serine, [4,5-3H]isoleucine or [2,3-3H]alanine. Amino acid-sequence analyses showed that over 90% of the total cell-free product was one homogeneous protein, which corresponds to the MOPC-63 L-chain precursor. In this precursor an extra piece, 20 amino acid residues in length, precedes the N-terminus of the mature L chain. The extra piece contains one methionine residue at the N-terminus, six leucine residues, which are clustered in two triplets at positions 6, 7, 8 and 11, 12, 13, one proline residue at position 16, and one serine residue at position 18. The closely gathered leucine residues, as well as their abundance (30%), suggest that the extra-piece moiety is hydrophobic. In the precursors, the extra piece is coupled to the variable region of the L chain. Partial sequences of precursors of L chains of the same and different subgroups that were labelled with the above six radioactive amino acids indicate that the extra piece is part of the variable region. Thus the precursors of MOPC-63 and MOPC-321 L chains, which are of the same subgroup, have extra pieces of identical size (20 residues), and so far their partial sequences are also identical (see above). On the other hand, in the precursor of MOPC-41 L chain, which is of a different subgroup, the extra piece is 22 residues in length. Further, the sequence of the MOPC-41 extra piece differs in at least ten positions from sequences of the extra pieces of the precursors of MOPC-63 and MOPC-321 L chains.
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PMID:Amino acid-sequence variability at the N-terminal extra piece of mouse immunoglobulin light-chain precursors of the same and different subgroups. 82 40

From collected data on variable region sequences of heavy chains of immunoglobulins, the probability of random associations of any two amino-acid residues in the complementarity-determining segments was computed, and pairs of residues occurring significantly more frequently than expected were selected by computer. Significant associations between Phe 32 and Tyr 33, Phe 32 and Glu 35, and Tyr 33 and Glu 35 were found in six proteins, all of which were mouse myeloma proteins which bound phosphorylcholine (= phosphocholine). From the x-ray structure of McPC603, Tyr 33 and Glu 35 are contacting residues; a seventh phosphorylcholine-binding mouse myeloma protein also contained Phe 32 and Tyr 33 but position 35 had only been determined as Glx and thus this position had not been selected. Met 34 occurred in all seven phosphorylcholine-binding myeoma proteins but was also present at this position in 29 other proteins and thus was not selected; it is seen in the x-ray structure not to be a contacting residue. The role of Phe 32 is not obvious but it could have some conformational influence. A human phosphorylcholine-binding myeloma protien also had Phe, Tyr, and Met at positions 32, 33, and 34, but had Asp instead of Glu at position 35 and showed a lower binding constant. The ability to use sequence data to locate residues in complementarity-determing segments making contact with antigenic determinants and those playing essentially a structural role would contribute substantially to the understanding of antibody specificity.
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PMID:Attempts to locate residues in complementarity-determining regions of antibody combining sites that make contact with antigen. 106 Nov 62

This paper describes the derivation of the primary structure of the major valine tRNA in the cytoplasm of mouse myeloma cells. Approximately 75% of the nucleotide sequence of this tRNA is also shared by the tRNA1-Val of yeast, this homology serving as a further indication of the extreme conservation of the structures of the tRNAs of different eukaryotic organisms. A novel feature of mouse myeloma tRNA1-Val is its loop IV sequence: -U-PSI-C-G-M1A-A-A-. This particular loop IV sequence has not previously been found in a tRNA structure. In addition, tRNA1-Val possesses some unusual nucleoside modifications. 5-Methyluridine (T) was not found to occur within loop IV of this tRNA, although this minor nucleoside is also absent from certain other mammalian tRNAs. Only one other tRNA, mammalian tRNAf-Met, has been found to possess 2-methylguanosine (m2G) in the position between the (b) and (c) stems of the cloverleaf. Numerous tRNAs have m2-2G in this location, and it would appear that the second methylation of this guanosine is characteristically absent from certain mammalian tRNA species.
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PMID:The primary structure of the major cytoplasmic valine tRNA of mouse myeloma cells. 109 87

The major form of methionine tRNA operational in the elongation of protein synthesis in mouse myeloma cells was purufied from these cells after they had been cultured in the presence of [32P]-phosphate. This [32P]tRNA4-Met species was then digested with T1 RNase or pancreatic RNase so as to obtain both complete and partial RNase digestion products. The nucleotide sequences of these fragments were analysed to enable the derivation of the complete primary structure of this tRNA. tRNA4-Met of mouse myeloma cells is 76 nucleotides in length and contains 15 modified nucleotides. It is the only tRNA yet sequenced which has been found to possess the minor nucleoside 2-methylguanosine (m2G) within the amino acid (a) stem, and also to have an anticodon (c) stem of only 4 and not 5 base-pairs. The loop IV sequence of eukaryotic initiator methionine tRNA (tRNAf-Met) species, -A-U-C-G-m1A-A-A-, IS NOT FOUND IN TRNA4-Met and is therefore absent from at least one of the methionine tRNAs functioning in polypeptide elongation in mammalian cells. This is consistent with the suggested importance of this loop structure in the initiator function of tRNAf-Met in eukaryotic organisms. Three distinct regions of the tRNA cloverleaf, the (b) stem, the anticodon loop (loop II), and loop III, are substantially conserved in structure between tRNAf-Met and tRNA4-Met of mouse myeloma cells. These regions of the structures of mammalian methionine tRNAs probably do not determine whether a certain tRNA-Met will function in the initiation or elongation of protein synthesis, although they might be important in tRNA-Met recognition if the different cytoplasmic tRNA-Met species of mammalian cells are aminoacylated by a single activating enzyme.
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PMID:The nucleotide sequence of a methionine tRNA which functions in protein elongation in mouse myeloma cells. 116 34

A recombinant myeloma NS1-derived clone was grown in chemostat cultures in Dulbecco's MEM/Ham's F12 (1:1) medium containing various concentrations of glucose, at a dilution rate of 0.028 h-1. Serum-supplemented cultures were virtually glucose-limited at a large range of glucose feed concentrations (0.7-5 mM). True glucose-limited cultures, however, were only established at low glucose supply levels to 1.3 mM at a maximum. In cultures obtained at higher glucose concentrations methionine was shown to be the growth-limiting compound. The pattern derived for serum-free chemostat cultures was similar, except that growth yields on glucose were much lower. Glucose was shown to be the growth-limiting substrate in cultures fed with media containing less than 4.5 mM glucose. Upon supplying glucose at higher concentrations such cultures presumably run into methionine and/or tryptophan limitation.
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PMID:Physiology of myeloma cells grown in glucose-limited chemostat cultures. 136 65

We report a method for introducing a glutamine synthetase (GS) selectable marker into myeloma cells in which transfectants are selected by growth in a glutamine-free medium. Vector amplification can subsequently be selected using the specific inhibitor of GS, methionine sulphoximine (MSX). Using this system, DNA sequences encoding a chimeric B72.3 IgG4 antibody were expressed from hCMV-MIE promoters in NSO myeloma cells. A cell line was isolated after a single round of selection for vector amplification which contains approximately 4 copies of the vector, secretes 10-15 pg/cell/day cB72.3 antibody during exponential growth and can accumulate 560 mg/l antibody in a fed-batch air-lift fermentation system. Productivity is stable in the absence of MSX selection.
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PMID:High-level expression of a recombinant antibody from myeloma cells using a glutamine synthetase gene as an amplifiable selectable marker. 136 77

It was demonstrated recently that substrates for protein N-methyltransferases (J. Najbauer and D. W. Aswad, 1990, J. Biol. Chem. 265, 12,717-12,721) and protein carboxyl methyltransferases (J. Najbauer, B. A. Johnson, and D. W. Aswad, 1991, Anal. Biochem. 197, 412-420) accumulate when rat PC12 cells are cultured in the presence of the methylation inhibitor, adenosine dialdehyde. In the present report, we have further characterized this phenomenon in PC12 cells and in two other, widely used cell types. Adenosine dialdehyde was found to increase the methyl-accepting capacity of proteins in human skin fibroblasts and mouse Sp2/0 myeloma cells. However, both the level of methyl incorporation in untreated cells and the amount of stimulation afforded by inhibitor treatment were substantially lower in these cells than in PC12 cells. All three cell lines accumulated methyl acceptor(s) at 17-21 kDa. The PC12 cells and the fibroblasts also exhibited stimulation of three apparently similar proteins in the 33- to 38-kDa region, where several arginine-methylated proteins involved in RNA processing would be expected. The optimal conditions for methylation of PC12 cell extracts with regard to pH, time of methylation, and S-[methyl-3H]adenosyl-L-methionine concentration were characterized. Increased methyl incorporation was detected after adenosine dialdehyde treatments as short as 2 h, and methylation of most substrates continued to increase as the time of treatment was extended to 72 h. The kinetics of accumulation varied from substrate to substrate. Fluorograms of two-dimensional gels of extracts from untreated PC12 cells incubated in the presence of S-[methyl-3H]adenosyl-L-methionine revealed patterns of methyl incorporation similar to those of treated cells, but longer exposure times were necessary (e.g., 35 days vs 7 days). These findings suggest that the inhibitor treatment works mainly by inhibiting the post- or cotranslational methylation of a "normal" array of cellular proteins.
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PMID:Analysis of stable protein methylation in cultured cells. 173 43

IgE antibodies are best known for their pathological role in allergy. The class-specific effector sites are located in the epsilon chains; these form covalent dimers via two cystine residues (Cys241 and Cys328) linking opposite C epsilon 2 domains. The nature and biological significance of the inter-epsilon chain disulfide-bond arrangement is unresolved. For structural and functional analysis site-specific mutations were introduced into the C epsilon 2 domain of recombinant human IgE. The introduction of an additional cyanogen bromide cleavage site (His246----Met) facilitated the identification of parallel disulfide bond pairing. This linkage was also confirmed for myeloma IgE PS by sequence determination of disulfide-linked C epsilon 2 dimers. Substitution of Cys241 and Cys328 by Ser does not destroy receptor binding, but reductive alkylation, or the replacement of Cys328 by Met, leads to loss of activity. This shows that covalent dimerization is not essential for IgE/receptor interaction and points to the importance of the structural integrity of the site surrounding Cys328, visualized in a new model of human Fc epsilon.
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PMID:The nature and importance of the inter-epsilon chain disulfide bonds in human IgE. 182 28

Primary amyloidosis and myeloma associated amyloidosis causes neuropathy in 10% of the cases, and hemodialysis associated amyloidosis causes carpal tunnel syndrome. However, most severe amyloid neuropathy is observed in familial amyloidotic polyneuropathy (FAP). FAP type I is an autosomal dominant systemic amyloidosis characterized by sensory dominant systemic amyloidosis characterized by dissociated sensory disturbance and autonomic dysfunction. Amyloid deposition is noted universally in endoneurium of peripheral nerve, especially prominent in sural, sciatic nerve, dorsal root ganglia and sympathetic ganglia. Moderate deposition was also noted in dorsal spinal root. Amyloid was absent in CNS. The number of small myelinated fibers is decreased. Unmyelinated axons are severely depleted and amyloid fibrils are observed around the wall of small vessels. Amyloid fibril protein consists of variant transthyretin (TTR:prealbumin) with one amino acid substitution of methionine-for-valine at position 30. Other types of FAP show another one point mutation in TTR molecule. Transgenic mouse model of FAP was produced by microinjecting cloned human variant TTR gene into mice. Amyloid were demonstrated in thyroid, kidney and intestine and so on, but not in peripheral nerve in these mice. Pathogenesis of neuropathy of FAP is not known, but mechanical compression to the nerve, ischemia and metabolic abnormality may play some role combined to cause of nerve fiber damage. The effect of deposition on physiochemical functions of the neuron and mechanism to accumulate in nervous system of the TTR remain to be elucidated.
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PMID:[Amyloid neuropathy]. 196 18


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