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)

The localization of the protein tyrosine kinase pp60c-src to the plasma membrane and to the membrane of secretory vesicles in neurally derived bovine chromaffin cells has suggested that tyrosine phosphorylations may be associated with the process of secretion. In the present study we have identified two cytosolic proteins of approximately 42 and 45 kD that become phosphorylated on tyrosine in response to secretagogue treatment. Phosphorylation of these proteins reached a maximum (3 min after stimulation) before maximum catecholamine release was observed (5-10 min after stimulation). Both secretion and tyrosine phosphorylation of p42 and p45 required extracellular Ca2+. Tyrosine-phosphorylated proteins of similar Mr have previously been identified in 3T3-L1 adipocytes stimulated with insulin (MAP kinase; Ray, L. B., and T. W. Sturgill. 1987. Proc. Natl. Acad. Sci. USA. 84:1502-1506) and in avian and rodent fibroblasts stimulated with a variety of mitogenic agents (Cooper, J. A., D. F. Bowen-Pope, E. Raines, R. Ross, and T. Hunter. 1982. Cell. 31:263-273; Nakamura, K. D., R. Martinez, and M. J. Weber. 1983. Mol. Cell. Biol. 3:380-390). Comparisons of the secretion-associated 42-kD protein of chromaffin cells with the 42-kD protein of Swiss 3T3 fibroblasts and 3T3-L1 adipocytes provide evidence that these three proteins are highly related. This evidence includes comigration during one-dimensional SDS-PAGE, cochromatography using ion exchange and hydrophobic matrices, similar isoelectric points, identical cyanogen-bromide peptide maps, and cochromatography of MAP kinase activity with the tyrosine-phosphorylated form of pp42. This protein(s), which appears to be activated in a variety of cell types, may serve a common function, perhaps in signal transduction involving a cascade of kinases.
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PMID:A 42-kD tyrosine kinase substrate linked to chromaffin cell secretion exhibits an associated MAP kinase activity and is highly related to a 42-kD mitogen-stimulated protein in fibroblasts. 168 32

Erythrocytes (E) from patients with paroxysmal nocturnal hemoglobinuria (PNH) lack decay-accelerating factor (DAF) and this partly causes increasing susceptibility of the E to complement. Several reagents have been used to convert normal E to the complement-sensitive (PNH-like) cells. The relationship between DAF amounts and complement susceptibility of these PNH-like cels has been examined. Of the reported reagents for preparation of PNH-like cells, 2-amino-ethylisothiouronium bromide (AET), papain, and periodate efficiently converted normal E to the complement-sensitive cells, but only papain reduced the quantity of DAF on the cells. Further, of the proteases we tested only papain cleaved DAF to liberate its major fragment from the cells. The papain-treated cells lysed in a similar fashion to PNH cells as the serum concentration increased. The major papain-digested product of DAF had Mr, 55,000, lacked hydrophobicity, and retained the ability to inhibit the C3 convertases. These findings suggest that papain allows liberation from cells of functional domains as well as most of the antigenic epitopes of DAF to generate a PNH-like cell.
Mol Immunol 1990 Jan
PMID:Proteolytic elimination of decay-accelerating factor (DAF): lytic abnormality coincides with removal of DAF in papain-treated human erythrocytes. 169 Mar 49

A 1735 bp cDNA for human placental cytokeratin 8 is described which encompasses the entire coding sequence as well as 33 and 250 base pairs of 5'- and 3'-untranslated region, respectively. The level of cytokeratin 8 mRNA in various fetal tissues and placentae of different gestational ages was determined as were the effects of 8-bromo-cAMP on cytokeratin 8 mRNA in primary cultures of cytotrophoblasts and JEG-3 choriocarcinoma cells. Cytokeratin 8 mRNA was abundant in fetal small intestine, placenta, pancreas, lung, liver, and kidney. Levels of cytokeratin 8 mRNA in placenta increased slightly during pregnancy. 8-Bromo-cAMP suppressed cytokeratin 8 mRNA in primary cultures of cytotrophoblasts, whereas the cAMP analog increased mRNA levels in JEG-3 cells, revealing differential regulation of this mRNA in normal and transformed trophoblastic cells.
Mol Endocrinol 1990 Mar
PMID:Cloning and sequence of cDNA for human placental cytokeratin 8. Regulation of the mRNA in trophoblastic cells by cAMP. 169 65

The effect of intercalating drugs (the anthracycline group of antibiotics, ethidium bromide, actinomycin D) on stepwise melting of DNA was studied by differential scanning calorimetry (DSC). The DSC DNA melting profile of plasmid pJL3-TB5 DNA (5277 base-pairs in length) consists of seven peaks, and all the intercalators caused shifting of these peaks, particularly those formed at the high temperature ranges, to the higher temperature ranges in a characteristic manner depending upon the binding strength of the drug. The analysis of the anthracycline group of antibiotics, such as aclacinomycin A, daunomycin, adriamycin and pyrarubicin, indicates that the difference in binding is due to the sugar moiety at position O-7 of the chromophore in these antibiotics. Analysis on the basis of the helix-coil transition theory suggests that the anthracycline group of antibiotics interact preferentially with the 5'-CG-3' sequences. The effect of various DNA-binding drugs other than intercalators on stepwise melting of DNA was then studied by DSC. The representative drugs examined were distamycin A, peplomycin, cis-dichlorodiamine-platinum(II) (cis-DDP or cis-Platin) and mitomycin C, which differ in their mode of interaction with DNA; namely, minor groove binding, strand cleavage and intrastrand or interstrand cross-linking. Distamycin A caused shifting of the DSC peaks at the low temperature ranges to a higher temperature range, whereas peplomycin and cis-DDP caused shifting of all the DSC peaks to form a broad peak at a lower temperature range, suggesting that the DSC DNA melting profiles are affected in a characteristic manner depending upon the interaction mode of the drug.
J Mol Biol 1990 Sep 20
PMID:Differential scanning calorimetric study of the effect of intercalators and other kinds of DNA-binding drugs on the stepwise melting of plasmid DNA. 169 88

The effects of guanosine 3':5'-cyclic monophosphate (cGMP) on cardiac contraction are not established. Using isolated electrically-stimulated ferret papillary muscle at 29 degrees C, 2.0 mM calcium we investigated the effects of 8-Bromo-cGMP on (a) basal contraction for comparison with the effects of reduction in extracellular calcium or of reduction in resting muscle length; (b) contraction of preparations stimulated by isoprenaline, the dihydropyridine calcium agonist Bay K8644 or post-extrasystolic potentiation. 8-Bromo-cGMP (0.1 mM) induced a small significant reduction in isometric twitch tension (TT) (7%), isotonic shortening (PS) (6%) and in twitch duration, but had no effect on maximum unloaded shortening velocity (Vmax) or rate of tension development (+dT/dt). Reduction in muscle length induced a similar immediate effect on contraction. Reduction of extracellular calcium (2.0 mM to 1.25 mM) reduced TT by 24% and PS by 14% as well as Vmax (19%) and +dT/dt (29%), but did not alter twitch duration. Bay K8644 (0.01 to 10 microM) produced increases in TT, +dT/dt, PS and twitch duration each of which was significantly reduced in the presence of 8-Bromo-cGMP (0.1 mM). 8-Bromo-cGMP had no effect on the responses to isoprenaline 1 nM to 100 microM--which increased TT, +dT/dt and PS but markedly reduced twitch duration--nor on post-extrasystolic potentiation which increased TT and +dT/dt but slightly reduced twitch duration. These results show that 8-Bromo-cGMP induces changes similar to the immediate effects of reduction in resting muscle length, and reduces the positive inotropic effects of Bay K8644 but not those of isoprenaline or post-extrasystolic potentiation.
J Mol Cell Cardiol 1991 Jan
PMID:Effects of 8-bromo-cyclic GMP on contraction and on inotropic response of ferret cardiac muscle. 170 73

Alphafetoprotein (AFP), an oncofetal antigen, plays very important roles in the early embryonic life and oncogenesis. Under various physiological and pathological conditions AFP exhibits microheterogeneity, probably as a result of differential expression of its epitopes. To analyse the epitopes we have developed a panel of monoclonal antibodies against human AFP purified by a new and efficient method using an immunoadsorbent consisting of polyclonal antibodies immobilized on cyanogen bromide activated Sepharose. Clones producing antibodies of various isotypes, e.g. IgG1, IgG2a, IgG2b, IgA and IgM have been subcloned and characterized. The antibodies showed high avidity for AFP (with half-maximal binding concentrations between 0.012 and 3.87 nM). Mutual inhibition efficiencies of a panel of 14 monoclonal antibodies were determined by RIA. Based on these inhibition data a computer program was used to group these antibodies with respect to their "epitope specificity distance". As a result of this grouping, clones have been identified which can recognize at least five different epitopes on AFP. This panel of antibodies may be very useful for analysis of the epitopic variation of AFP under various physiological and pathological conditions.
Mol Immunol 1991 Jul
PMID:Epitope analysis of the oncofetal antigen alphafetoprotein using monoclonal antibodies. 171 94

Numerous RNA species of different length and nucleotide sequence grow spontaneously in vitro in Q beta replicase reactions where no RNA templates are added deliberately. Here, we show that this spontaneous RNA synthesis by Q beta replicase is template directed. The immediate source of template RNA can be the laboratory air, but there are ways to eliminate, or at least substantially reduce, the harmful effects of spontaneous synthesis. Solitary RNA molecules were detected in a thin layer of agarose gel containing Q beta replicase, where they grew to form colonies that became visible upon staining with ethidium bromide. This result provides a powerful tool for RNA cloning and selection in vitro. We also show that replicating RNAs similar to those growing spontaneously are incorporated into Q beta phage particles and can propagate in vivo for a number of phage generations. These RNAs are the smallest known molecular parasites, and in many aspects they resemble both the defective interfering genomes of animal and plant viruses and plant virus satellite RNAs.
J Mol Biol 1991 Nov 05
PMID:On the nature of spontaneous RNA synthesis by Q beta replicase. 171 19

Four clones producing monoclonal antibodies inhibiting enzymatic activity were used to localize the functionally important antigenic determinants of T7 RNA polymerase. All antibodies were shown to bind to C-terminal fragment of the protein (residues 589-883). The competition studies showed the specificity of the three antibodies toward one epitope and the fourth antibody to another one. By means of limited cleavage of the RNA polymerase with cyanogen bromide with subsequent electrophoretic separation and immunoblotting the peptides containing antigenic determinants were localized. These are Met861-Ala883 for antibody 4H8 and Met750-Met832 for antibodies 9B2, 3H11 and 2A2.
Mol Biol (Mosk)
PMID:[Topography of bacteriophage T7 RNA polymerase using monoclonal antibodies]. 172 77

A rapidly acquired partial resistance to the replicase antagonist, ethidium bromide (EB), seen by Spiegelman and coresearchers in Q beta RNA variants competitively replicating under defined conditions in vitro, reflected existence of a pool of mutant RNA molecules, preadapted to EB, and their cross-propagation from the pre-EB optimum species, MDV-1, and from other kindred variants, some of which remained undetected, according to this quantitative analysis of midivariant RNA replication kinetics. DNAlike features of their evolution, such as the cloning of variants from an MDV-1 subtype and a compliance with the fundamental theorem of natural selection, resulted from the suppression, both real and apparent, of intrinsic RNA heterogeneity through sampling and detection methods, and also by the ascendency of self-propagation over cross-propagation with advancement of a superior variant. The deficit in mean polymer fitness, compared with optimum levels, determines the lower limit of this heterogeneity. Stability conditions for frequency equilibrium and strategies for counteracting viral drug resistance have been considered.
J Mol Evol 1991 Oct
PMID:Kinetics of rapid RNA evolution in vitro. 172 7

A lambda gt11 cDNA library, constructed from poly(A)+ RNA isolated from immature rice seed endosperm, was screened with affinity-purified antibodies against the rice storage protein called alpha-globulin (previously), or the 19 kDa globulin (our term). A positive clone was isolated and sequenced and shown to encode a 21 kDa precursor for the 19 kDa globulin, based on the identity of portions of the inferred amino acid sequence and the sequence of three cyanogen bromide peptides of the 19 kDa globulin. Analysis of genomic DNA by Southern blotting using the cDNA clone probe revealed one hybridizing band in Eco RI, Hind III, and Bam HI digests. This strongly suggests that the 19 kDa globulin is encoded by a single-copy gene. Because of its single-copy nature and its abundance of Arg and lack of Lys, the 19 kDa rice globulin appears to be a particularly attractive target for genetically engineering increased Lys content in rice seeds.
Plant Mol Biol 1992 Jan
PMID:A novel cereal storage protein: molecular genetics of the 19 kDa globulin of rice. 173 68


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