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)

Disulphide-rich proteins of widely differing functions were aligned with the aid of their half-cystinyl residues. This led to the grouping of ribonuclease, phospholipase A, lysozyme, snake venom toxins, bee and scorpion venom peptides, and the plant proteins potatoe carboxypeptidase inhibitor, ragweed pollen allergen, mistletoe toxins and pineapple sulfhydryl protease inhibitor into one super-family of proteins. Very few deletions/insertions were needed to effect alignment and probabilities were calculated for random occurrence of the matches that were found.
J Mol Evol 1977 Aug 05
PMID:Homology of functionally diverse proteins. 89 36

Previous results showed that cell disintegration in the fungus Podospora anserina occured through the action of two proteases, enzymes whose messengers were normally latent during the extension stage of the thallus. We selected three mutant strains in which the constitutive activity of the protease messengers was expressed by an arrest of growth early in development (10 to 30 hours after spore germination) and a reaction of cell disintegration, in the thallus, suppressible with beta-phenyl pyruvic acid, a protease inhibitor. The mutant character is recessive in one strain. In the case of the two strains in which the mutant trait is dominant, reversion studies have revealed that the deregulation resulted from the specific interaction between two genes and we have succeded in creating two non allelic incompatibility systems comparable to the non allelic gene interactions responsible for the incompatibility phenomena found between wild type races. We know, on the whole, that 11 loci are involved in the regulation of the proteases: five were revealed as incompatibility loci and six were discovered from investigations on four self-lysing mutant strains. It is suspected that all these genes act at the post-transcriptionnal level of the synthesis of specific proteolytic enzymes. We propose that the products of two genes act as "repressors" to prevent the protease messengers from being constitutively translated and that the products of the nine remaining genes exert a positive control by inducing translation, at the appropriate time, through the action of effectors resulting from specific interloci cooperation.
Mol Gen Genet 1976 Mar 22
PMID:Regulation of proteolytic enzymes in Podospora anserina: selection and properties of self-lysing mutant strains. 127 46

Two antipeptide antibody preparations were raised against deduced amino acid sequences within the presumed second extra-cellular loop (antibody TP/1) and the carboxyl-terminal domain (antibody TP/2) of the canine-derived A2 adenosine receptor (A2AR) cDNA species termed RDC8. Immunoblotting of canine liver plasma membranes with both TP/1 and TP/2 identified a single band of 52 kDa, which co-migrated with 125I-2-[4-[2-[2-[(4- azidophenyl)methylcarbonylamino]ethylaminocarbonyl]ethyl] phenyl]ethylamino-5'-N-ethylcarboxamidoadenosine-labeled receptor. However, in membranes prepared from canine striatum, photoaffinity labeling and immunoblotting with TP/2, but not TP/1, revealed a single band of 34 kDa; the identity of the band observed on the immunoblot as an A2AR was confirmed by the ability of TP/2 to specifically immunoprecipitate photoaffinity-labeled receptor from crude canine striatal membranes. The size difference between liver and striatal A2ARs was not due to tissue-specific proteolysis, because membranes from striatum were prepared with a protease inhibitor cocktail previously shown to be effective in inhibiting endogenous A2AR proteolysis during membrane preparation. Also, the protease-sensitive carboxyl-terminal region of the receptor had remained intact, because the peptide used to raise TP/2 antibodies resides in this domain of the molecule. The difference in size was also not due to a greater carbohydrate content of the liver receptor, because treatment of liver and striatal membranes with endoglycosidase F produced small mobility shifts for both receptors. Removal of N-linked carbohydrate chains also did not alter the inability of TP/1 to recognize the striatal A2AR. Hence, we conclude that the A2AR present in liver, which displays the predicted immunoreactivity of RDC8, is immunologically distinct from the A2AR expressed in striatum and that the latter may represent an additional A2AR subtype.
Mol Pharmacol 1992 Sep
PMID:Immunological identification of A2 adenosine receptors by two antipeptide antibody preparations. 132 41

The origin of beta-amyloid deposited in senile plaques in Alzheimer's disease (AD) is not known. We compared the expression of protein precursor of beta-amyloid (APP) in the cell types involved in plaque formation. The levels of APP mRNA were determined in primary rat neurons and glial cells in culture, human endothelial cells and in a murine brain-derived endothelial cell line. Northern blot analysis was performed using an APP cDNA probe to detect the general APP sequence and an oligonucleotide (40 mer) complementary to the sequence of the Kunitz protease inhibitor (APP-KPI). The APP mRNA transcripts were abundant in all three cell types. The highest level of APP, normalized to beta-actin mRNA content, was expressed in neurons, followed by glial cells, where the APP expression was similar (94%) while in endothelial cells was lower (53%). The proportion between APP-KPI mRNA and total APP mRNA was high in endothelial, intermediate in glial and low in neuronal cells. We compared the effects of exposure to interleukin-1 (IL-1), a cytokine involved in several biological processes and elevated in AD, on APP mRNA expression in neuronal, glial and endothelial cells. In human endothelial and in brain-derived murine endothelial cells we observed a similar increase (50%) of total APP mRNA or APP-KPI mRNA after treatment with human recombinant IL-1 beta. In neuronal cells, IL-1 (200 ng/ml) substantially increased APP mRNA (175%), detected with both probes. In glial cells, the expression of APP mRNA did not appear to be altered by IL-1 (50-400 ng/ml). The results suggest a role of IL-1 in the neuronal mechanisms related to beta-amyloid protein deposition in AD.
Brain Res Mol Brain Res 1992 Nov
PMID:Expression of amyloid precursor protein mRNAs in endothelial, neuronal and glial cells: modulation by interleukin-1. 133 90

Alzheimer's Disease (AD), a disorder of unknown etiology, is the most common form of adult-onset dementia and is characterized by severe intellectual deterioration. The definitive diagnosis of AD is made by postmortem examination of the brain, which reveals large quantities of neurofibrillary tangles (NFT) and senile plaques within the parenchyma. The NFT are composed of paired helical filaments associated with several cytoskeletal proteins. The primary protein component of senile plaques is beta/A4 amyloid, a 42-43 amino acid peptide derived from a much larger molecule, the amyloid precursor protein (APP). Vascular beta/A4 amyloidosis is also prevalent in the disease. The mechanism by which beta/A4 amyloid accumulates in the AD brain is unknown. Recent research has demonstrated that the precursor molecule, APP, is a transmembrane protein with a large extracytoplasmic domain, a membrane spanning region that includes the portion that gives rise to beta/A4 amyloid, and a short intracytoplasmic domain. The precursor has multiple forms among which are those that differ by a variable length insert within the extracytoplasmic domain. The insert has sequence homology to the family of Kunitz protease inhibitor proteins. Cellular and animal models have been developed to study the nature of APP processing and the biological and behavioral consequences of beta/A4 amyloidosis. The results of such studies indicate that the normal processing of APP involves enzymatic cleavage of the molecule within the beta/A4 amyloid region, thus preventing the accumulation of beta/A4 in the normal brain. The factors leading to abnormal processing of APP, and consequent beta/A4 amyloid accumulation within the AD brain, have yet to be identified. In cell culture, the biological effects associated with beta/A4 amyloid include neurotrophic and neurotoxic activities, while the peptide has also been shown to have dramatic behavioral effects in animal models.
J Mol Neurosci 1992
PMID:Molecular and cellular biology of Alzheimer amyloid. 162 58

The nucleus basalis of Meynert was lesioned by infusion of N-methyl-D-aspartate (NMDA) unilaterally in adult rat brain. Seven days post lesion we observed that polysomes isolated from the cerebral cortex affected by the lesion synthesized 2.6-fold greater amounts of the Alzheimer amyloid precursor protein (AAPP) compared to the nonlesioned side of the same rat brain. This increase exhibited specificity to AAPP in that overall protein synthesis was not altered by the lesion. The increase of AAPP did not alter the ratio of AAPP isotypes in rat brain (in which AAPP 695, which is lacking the protease inhibitor insert remains the predominant form). The increased synthesis did not result in the apparent accumulation of mature AAPP. These results indicate that a cholinergic lesion which models many of the neurochemical changes observed in Alzheimer's disease induces the expression of AAPP in a major projection region, the cerebral cortex.
Brain Res Mol Brain Res 1991 May
PMID:Increased biosynthesis of Alzheimer amyloid precursor protein in the cerebral cortex of rats with lesions of the nucleus basalis of Meynert. 164 69

The beta-amyloid precursor protein (APP) is involved in the degenerative and regenerative neural changes associated with aging and Alzheimer's disease. We studied the regulation of APP gene expression in a paradigm of degeneration and regeneration, the axotomized rat sciatic system. The sciatic nerves of rats were crushed and at intervals between 4 and 60 days, the affected dorsal root ganglia and spinal cord segments were processed for Northern analysis and in situ hybridization to evaluate various APP mRNA species. After nerve crush, dorsal root ganglia APP mRNA levels are increased for both APP695 (695 amino acids) and APPKPI (Kunitz protease inhibitor). Following reinnervation, APP695 returns to baseline but APPKPI remains elevated. In spinal cord there is a decrease of APP695, which returns to baseline following reinnervation. If regeneration is prevented, the initial phase of post-axotomy response for all APP forms persists for at least 60 days in both dorsal root ganglia and spinal cord. In situ hybridization confirms that the changes are referable to neurons. These findings indicate that neuron-target interactions are important in APP gene regulation; that the APP695 and APPKPI transcripts are differentially regulated following neuronal injury; and that different neuronal populations regulate APP expression in a cell-type specific manner.
Brain Res Mol Brain Res 1991 Jul
PMID:Beta-amyloid precursor protein gene is differentially expressed in axotomized sensory and motor systems. 165 58

The alpha 1-protease inhibitor (alpha 1-PI) proteins of mice are encoded by a group of genes whose members are expressed coordinately in a liver-abundant pattern and are regulated primarily at the transcriptional level. To better understand the developmental and tissue-specific regulation of this gene family, one member that is analogous to the human alpha 1-antitrypsin gene was chosen for study. Deletional analysis of the upstream regulatory region of this gene was performed, spanning from -10 kilobases to -80 base pairs relative to the transcriptional start site. Two functional positive cis-acting elements within the 522 bases immediately upstream of the start site for transcription were shown to modulate the level of expression from this promoter when introduced into human or mouse hepatoma cells, and a third region acted as a negative regulatory element in that its deletion resulted in a two- to sixfold increase of expression of a transfected minigene construct. Sequence comparison between the regulatory domains of two mouse alpha 1-PI genes and the human alpha 1-antitrypsin gene showed that the mouse gene contains a novel positive cis-acting element which is absent in human gene and that a specific eight-base-pair difference between species results in a strong positive cis-acting element in the human gene acting as a negative element in the mouse gene. An enhancer located approximately 3,000 base pairs upstream of the major start site for transcription was also identified. This element is position and orientation independent. Several different DNA-protein binding assays were used to demonstrate that each DNA segment with functional significance in transfection assays interacts specifically with proteins found in adult mouse liver nuclei. The major positive-acting element appeared to be specifically recognized by nuclear proteins found only in tissues that express alpha 1-PI, while the negative element binding proteins were ubiquitous. Thus, the distal regulatory domain including bases -3500 to -133 of this murine alpha 1-PI gene family member is more complex than was previously demonstrated. It is composed of a set of at least three additional functional cis-acting regulatory elements besides those which have been mapped by others and has a far upstream enhancer.
Mol Cell Biol 1990 Jun
PMID:Negative and positive cis-acting elements control the expression of murine alpha 1-protease inhibitor genes. 169 57

To clarify the role of thrombin in fibroblast growth and the development of pulmonary fibrosis in bleomycin-induced interstitial lung disease, we examined the relationship of thrombin activity to fibroblast growth-stimulating activity (FGA) in bronchoalveolar lavage (BAL) fluid from bleomycin-treated rats. Male Wistar rats were given a single intratracheal injection of bleomycin, BAL was performed 2, 6, and 15 days later, and the BAL fluid was assayed for thrombin activity and FGA. Higher FGA than the control value was detected in the BAL fluid from rats on day 6 after bleomycin administration. In bleomycin-treated rats, thrombin activity in the BAL fluid was significantly elevated on day 2 and maximal on day 6. The FGA of the BAL fluid from bleomycin-treated rats on day 6 was significantly decreased by its treatment with various thrombin inhibitors, such as alpha 1-protease inhibitor, antithrombin III, hirudin, and MD-805. In our assay, purified rat thrombin also showed FGA in vitro, and its FGA was inhibited by the same concentrations of these thrombin inhibitors as those inhibiting the activity in the BAL fluid. On ammonium sulfate fractionation, most of the thrombin activity was recovered in the fraction of 35 to 50% saturation in which most of the FGA was detected. These results suggest that the FGA of the BAL fluid from bleomycin-treated rats was at least partly due to thrombin is responsible, at least in part, for fibroblast growth and pulmonary fibrosis in bleomycin-induced interstitial lung disease.
Am J Respir Cell Mol Biol 1991 Jul
PMID:Thrombin enhances lung fibroblast proliferation in bleomycin-induced pulmonary fibrosis. 171 76

Alph alpha 2-macroglobulin (alpha 2M), a protease inhibitor which also binds growth factors and cytokines, is temporally expressed in association with remodelling phenomena in the ovary: ovulation and luteinization. Specific hormonal, cellular, subcellular, and molecular events regulating alpha 2M mRNA and protein have been analyzed during follicular growth, ovulation, and luteinization using complementary in vivo and in vitro models. Data demonstrate that alpha 2M mRNA and protein are synthesized in thecal cells of developing follicles in response to low levels of LH. Conversely, alpha 2M mRNA and protein are only synthesized by granulosa cells of follicles that have been stimulated to luteinize either in vivo by the LH surge or in vitro by FSH and testosterone and are also exposed to PRL. The obligatory requirement for PRL is specific; associated with increased numbers of PRL-binding sites; mediated by time-dependent appearance of alpha 2M in the endoplasmic reticulum (12 h), Golgi apparatus (24 h), and secretion vesicles (48 h); and involves in part increased transcription of the alpha 2M gene.
Mol Endocrinol 1991 Sep
PMID:Regulation of alpha 2-macroglobulin by luteinizing hormone and prolactin during cell differentiation in the rat ovary. 172 70


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