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)

Nicotinic acetylcholine receptor (AChR) is a transmembrane protein belonging to the superfamily of rapid, ligand-operated channels. Theoretical models based on thermodynamic criteria assign portions of the polypeptide chains to the lipid bilayer region. From an experimental point of view, however, the relationship between the two moieties remains largely unexplored. Current studies from our laboratory are aimed at defining the structural, dynamic, and functional relationship between membrane lipids and AChR. We are particularly interested in establishing the characteristics of and differences between the lipids in each leaflet of the bilayer and the belt or "annular" lipids immediately surrounding AChR and the bulk bilayer lipids. We are also interested in determining the possible implications of lipid modifications on AChR channel properties. Toward these ends, fluorescence and other spectroscopic techniques, together with biochemical analyses and patch-clamp studies, are currently being undertaken. Correlations can be established between structural aspects of phospholipid packing in the immediate perimeter of AChR and other properties of these annular lipids revealed by dynamic spectroscopic and molecular modeling techniques. Lipid compositional analyses of the clonal muscle cell line BC3H-1 and chemical modification studies have been carried out by incubation of intact cells in culture and of membrane patches excised therefrom with liposomes of different lipid composition. These studies have been combined with electrophysiological measurements using the patch-clamp technique, with the aim of determining the possible effects of lipids on the channel properties of muscle-type AChR. A variety of experimental conditions, involving polar head and fatty acyl chain substitution of phospholipids and cholesterol incorporation, are being assayed in the BC3H-1 cells.
Mol Neurobiol 1992
PMID:Structural and functional crosstalk between acetylcholine receptor and its membrane environment. 128 35

We have isolated a bovine prolactin (bPRL) receptor cDNA from an endometrial cDNA library, which predicts a 557 amino acid transmembrane protein similar to the long forms of other characterized prolactin receptors. The predicted cytoplasmic domain is slightly truncated primarily by a stop codon located 36 codons 5' from the stop utilized in the human hepatic transcript. When expressed in COS cells, this cDNA was shown to encode a protein which bound bovine placental lactogen (bPL) and bPRL with nearly equal affinity (KD for bPL, 2.03 x 10(-10) M; bPRL, 3.07 x 10(-10) M). Northern analysis demonstrated multiple transcripts, with maternal liver, corpus luteum, intestine, endometrium and fetal liver containing a major transcript of about 3.8 kb, and maternal corpus luteum and endometrium, a second sized transcript of apparently equal abundance of 4.4 kb. This difference did not appear to be within the coding region. Primer extension analysis of maternal hepatic and endometrial transcripts revealed considerable heterogeneity. Examination of the distribution of prolactin and growth hormone receptor transcripts at mid-pregnancy by semi-quantitative reverse transcriptase polymerase chain reaction showed that both are widespread in bovine fetal and placental tissues. This isolation of bovine prolactin receptor cDNA, and description of receptor distribution will facilitate study of the action of the placental and pituitary members of this gene family during pregnancy.
Mol Cell Endocrinol 1992 Nov
PMID:Molecular cloning of the bovine prolactin receptor and distribution of prolactin and growth hormone receptor transcripts in fetal and utero-placental tissues. 133 25

The c-erbB-2/neu gene encodes a transmembrane protein of 185 kDa (p185) with tyrosine kinase activity and extensive sequence homology to epidermal growth factor receptor. Amplification and overexpression of the c-erbB-2/neu gene has been shown in certain human tumors and is postulated to be important in human carcinogenesis. High levels of expression of the c-erbB-2/neu gene have been reported in non-small-cell lung cancer (NSCLC) cell lines and primary tumors from the United States. Since geographical and cultural factors may contribute to the development of certain types of cancer, we examined p185 examined p185 expression in 120 tumors from Chinese patients with lung cancers of different cell types and used immunohistochemical staining to determine the extent and general significance of p185 expression in human primary lung cancer. Our results demonstrate that 58.8% of the NSCLCs expressed p185 and that expression of p185 was observed only in NSCLC and not in small-cell lung cancers. Thirty-three of 41 adenocarcinomas and 24 of 55 squamous cell carcinomas among the NSCLCs examined were found to express p185 at levels different from those of normal lung. For the squamous cell carcinomas, p185 expression was correlated with lymph node metastasis (P less than 0.01), but for the adenocarcinomas, it was not (P greater than 0.05). In addition, expression of p185 in NSCLC was significantly more frequent in patients in advanced clinical stages. Our findings indicate that p185 expression is a frequent event and a general phenomenon in NSCLC and is correlated with poor clinical prognostic indicators, suggesting that expression of p185 may be of potential prognostic importance in NSCLC.
Mol Carcinog 1992
PMID:Overexpression of the c-erbB-2/neu-encoded p185 protein in primary lung cancer. 135 Jan 98

The c-kit ligand, KL, and its receptor, the proto-oncogene c-kit are encoded, respectively, at the steel (Sl) and white spotting (W) loci of the mouse. Both Sl and W mutations affect cellular targets in melanogenesis, gametogenesis, and hematopoiesis during development and in adult life. Although identified as a soluble protein, the predicted amino acid sequence of KL indicates that it is an integral transmembrane protein. We have investigated the relationship between the soluble and the cell associated forms of KL and the regulation of their expression. We show that the soluble form of KL is generated by efficient proteolytic cleavage from a transmembrane precursor, KL-1. An alternatively spliced version of KL-1, KL-2, in which the major proteolytic cleavage site is removed by splicing, is shown to produce a soluble biologically active form of KL as well, although with somewhat diminished efficiency. The protein kinase C inducer phorbol 12-myristate 13-acetate and the calcium ionophore A23187 were shown to induce the cleavage of both KL-1 and KL-2 at similar rates, suggesting that this process can be regulated differentially. Furthermore, proteolytic processing of both the KL-1 and KL-2 transmembrane protein products was shown to occur on the cell surface. The relative abundance of KL-1 and KL-2 is controlled in a tissue-specific manner. Sld, a viable steel allele, is shown to encode a biologically active secreted mutant KL protein. These results indicate an important function for both the soluble and the cell associate form of KL. The respective roles of the soluble and cell associated forms of KL in the proliferative and migratory functions of c-kit are discussed.
Mol Biol Cell 1992 Mar
PMID:Differential expression and processing of two cell associated forms of the kit-ligand: KL-1 and KL-2. 137 27

In most strains of Kluyveromyces lactis, respiratory function is not required for growth on glucose. However, some natural variant strains are unable to grow when respiration is blocked by specific inhibitors (Rag- phenotype). This phenotype is due to an allelic variation of the chromosomal gene RAG1. The sensitive variants have a recessive allele rag1. The RAG1 gene has been cloned by complementation of a rag1 strain from a genomic bank derived from a Rag+ strain. The nucleotide sequence of the cloned gene indicated that the RAG1 product was a sugar transporter protein. The amino acid sequence deduced from the gene structure contained the 12 hydrophobic segments typical of a transmembrane protein, and showed a high degree of homology with the GAL2 (galactose permease) and HXT2 (a high-affinity glucose transporter) proteins of Saccharomyces cerevisiae. In a rag1 null mutant, as in the natural rag1 variant, uptake of glucose at high external glucose concentrations was impaired. The RAG1 protein appears to correspond to a low-affinity glucose transporter. Transcription of the RAG1 gene, which was undetectable when cells were grown in glycerol, was induced by glucose. It is concluded that respiration-dependent growth on glucose of the Rag- variant strains is due to a defect in this inducible glucose transport system.
Mol Gen Genet 1992 May
PMID:Glucose transport in the yeast Kluyveromyces lactis. I. Properties of an inducible low-affinity glucose transporter gene. 160 78

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

CD45 is a high-molecular-weight transmembrane protein tyrosine phosphatase expressed only by nucleated cells of hematopoietic origin. To examine function, mouse CD8+ cytolytic T-cell clones were derived that had a specific defect in the expression of CD45. Northern (RNA) blot analysis indicates that the CD45 deficiency is due to either a transcriptional defect or mRNA instability. The CD45-deficient cells were greatly diminished in their ability to respond to antigen. All functional parameters of T-cell receptor signalling analyzed (cytolysis of targets, proliferation, and cytokine production) were markedly diminished. A CD45+ revertant was isolated, and the ability to respond to antigen was restored. These results support a central and immediate role for this transmembrane protein tyrosine phosphatase in T-cell receptor signalling.
Mol Cell Biol 1991 Sep
PMID:CD8+ T-cell clones deficient in the expression of the CD45 protein tyrosine phosphatase have impaired responses to T-cell receptor stimuli. 165 55

The retroviral oncogene v-erbB encodes a truncated form of the receptor for epidermal growth factor, an integral membrane protein-tyrosine kinase. By contrast, the oncogene v-src encodes a protein-tyrosine kinase that is a peripheral membrane protein. The morphologies and spectra of cells transformed by these two oncogenes differ. In an effort to identify the functional determinant(s) of these differences, we constructed and tested first deletion mutants of v-erbB and then chimeras between v-src and v-erbB. As reported previously, the absence of any membrane anchorage eliminated transformation by v-erbB. Anchorage of the cytoplasmic kinase domain of v-erbB to membranes with amino-terminal portions of the v-src protein permitted transformation. The phenotype and spectrum of transformation were those expected for v-erbB rather than for v-src. The transforming chimeras lost their biological activity if the signal for myristylation at the amino terminus of v-src was compromised by mutation. Biochemical fractionations revealed a correlation between transforming activity and the association of chimeric gene products with the membrane fraction of the cell. For reasons not yet apparent, the combined presence of membrane anchorage domains of v-src, and the transmembrane domain of v-erbB in the same chimera typically (but not inevitably) impeded transformation. Our results suggest that the specificity of transformation by v-erbB resides in the selection of substrates by the cytoplasmic domain of the gene product. The protein retains access to those substrates even when anchored to the membrane in the manner of a peripheral rather than a transmembrane protein.
Mol Cell Biol 1991 Sep
PMID:The amino-terminal 14 amino acids of v-src can functionally replace the extracellular and transmembrane domains of v-erbB. 167 56

We investigated the antigenicity of a highly conserved region in the transmembrane protein of the human immunodeficiency virus type 1 (HIV-1). In order to identify antigenically important residues, amino-acid sequences of synthetic peptides representing this region were varied systematically: single residues were omitted from the sequence of HIV-env 583-599; threonines were substituted for pairs of residues in HIV-env 581-599; the sequences of heptadeca-peptides were shifted by single residues. The peptides were tested in an enzyme immuno-assay against fourteen HIV-1 antibody-positive human sera, which were previously found to react with HIV-env 583-599, and against rabbit antisera to the peptides HIV-env 583-599 and 586-606. Substitutions as well as deletions in the sequence 589-596 (AVERYLKD) aborgated the antigenicity of the peptides with most of the human sera. Changes outside this sequence affected the reactivities differentially. Six overlapping dodeca-peptides, shifted in the sequence by single residues, lacked antigenicity in a competition assay, suggesting antigenic dependence on an ordered peptide conformation, which the longer peptides may preferentially assume. 19- and 21-mers with overlapping sequences competed to different extents with each other for binding to the antibodies of 3 human sera, illustrating that more than one antigenic structure in this narrow region can be recognized by a single polyclonal serum.
Mol Immunol 1991 Jun
PMID:A cluster of continuous antigenic structures in the transmembrane protein of HIV-1: individual patterns of reactivity in human sera. 171 46

Phosphoporin is a pore-forming transmembrane protein that spans the outer membrane of Escherichia coli and facilitates the diffusion of phosphates and phosphorylated compounds. Phosphoporin has been crystallized in several different crystal forms, although only one appears to be suitable for X-ray analysis. These crystals, which are hexagonal plates, diffract X-rays to 3 A resolution and belong to the space-group P6(3)22, with unit cell dimensions a = b = 121 A and c = 111 A.
J Mol Biol 1991 Dec 20
PMID:Crystallization and preliminary X-ray analysis of phosphoporin from the outer membrane of Escherichia coli. 172 57


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