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)

A single Ly-5 gene is known to generate a variety of transmembrane glycoprotein isoforms that distinguish various cell lineages and stages of differentiation within the hematopoietic developmental compartment of the mouse. Systems homologous to Ly-5 are known in rats and in humans. The complete exon-intron organization of the Ly-5 gene is described in this report. The Ly-5 gene occupies about 120 kilobases of chromosome 1 and comprises 34 exons, of which 32 (Ex-3 to Ex-34) are protein coding. Ex-1, Ex-2, and parts of Ex-3 and Ex-34 are untranslated. In all cDNA clones examined, either Ex-1 or Ex-2 was represented, but not both, implying that Ex-1 and Ex-2 in Ly-5 mRNA may be mutually exclusive. Primer extension and S1 nuclease protection mapping were used to identify initiation (cap) sites for transcription. The finding of putative cap sites for Ex-1 and Ex-2, and of corresponding TATA-like sequences, suggests the presence of two promoters. In both Ex-1+ and Ex-2+ cDNA clones the next exon is Ex-3, which has a translation-initiating codon. The intron between Ex-3 and Ex-4 is unusually long, about 50 kilobases. Evidence is given that Ex-5, like Ex-6 and Ex-7 (studied previously), is another alternative exon that is selectively programmed, alone or together with Ex-6 or Ex-7 or both, to generate actual or potential Ly-5 isoforms by alternative splicing.
Mol Cell Biol 1988 Nov
PMID:Organization of the Ly-5 gene. 321 Nov 31

A protein with an Mr of 145,000 (p145) was detected by antibodies to phosphotyrosine by Western blot (immunoblot) analysis. This protein was phosphorylated on tyrosine in a gastric carcinoma cell line. In cells that were metabolically labeled with 32Pi, this protein was phosphorylated on tyrosine and serine. p145 is a cysteine-rich transmembrane glycoprotein. The extracellular domain could be labeled by 125I under nonpermeating conditions and was cleaved by mild trypsin treatment of intact cells. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis under nonreducing conditions revealed a shift of p145 mobility to an apparent Mr of 190,000. After immunoprecipitation with phosphotyrosine antibodies, p145 displayed a strong associated protein kinase activity in vitro, becoming phosphorylated on tyrosine. There was no immunological cross-reaction between p145 and known tyrosine kinases. Both in vivo and in vitro tyrosine phosphorylations were unaffected by the addition of known growth factors. However, p145 was rapidly dephosphorylated in vivo when cells were exposed to low pH, a condition that is known to dissociate ligands from their receptors. These data suggest that p145 is associated with a protein tyrosine kinase activity which, in the tumor cell line studied, is activated by an as yet unidentified factor.
Mol Cell Biol 1988 Aug
PMID:p145, a protein with associated tyrosine kinase activity in a human gastric carcinoma cell line. 321 Nov 49

The biosynthesis of macrophage colony-stimulating factor 1 (CSF-1) was examined in mouse NIH-3T3 fibroblasts transfected with a retroviral vector expressing the 554-amino-acid product of a human 4-kilobase (kb) CSF-1 cDNA. Similar to results previously obtained with a 1.6-kb human cDNA that codes for a 256-amino-acid CSF-1 precursor, the results of the present study showed that NIH-3T3 cells expressing the product of the 4-kb clone produced biologically active human CSF-1 and were transformed by an autocrine mechanism when cotransfected with a vector containing a human c-fms (CSF-1 receptor) cDNA. The 4-kb CSF-1 cDNA product was synthesized as an integral transmembrane glycoprotein that was assembled into disulfide-linked dimers and rapidly underwent proteolytic cleavage to generate a soluble growth factor. Although the smaller CSF-1 precursor specified by the 1.6-kb human cDNA was stably expressed as a membrane-bound glycoprotein at the cell surface and was slowly cleaved to release the extracellular growth factor, the cell-associated product of the 4-kb clone was efficiently processed to the secreted form and was not detected on the plasma membrane. Digestion with glycosidic enzymes indicated that soluble CSF-1 encoded by the 4-kb cDNA contained both asparagine(N)-linked and O-linked carbohydrate chains, whereas the product of the 1.6-kb clone had only N-linked oligosaccharides. Removal of the carbohydrate indicated that the polypeptide chain of the secreted 4-kb cDNA product was longer than that of the corresponding form encoded by the smaller clone. These differences in posttranslational processing may reflect diverse physiological roles for the products of the two CSF-1 precursors in vivo.
Mol Cell Biol 1988 Nov
PMID:Differential processing of colony-stimulating factor 1 precursors encoded by two human cDNAs. 326 77

The transmembrane glycoprotein CD44 represents a family of molecules, all encoded by one gene. The variability of the isoforms is generated by alternative splicing of the nuclear RNA. Apart from the abundant standard form (CD44s), the variant isoforms (CD44v) are mostly restricted to epithelia. The present study demonstrates the expression of CD44s and CD44v isoforms in embryonic and fetal lungs and in normal and pathologically altered (pulmonary fibrosis after radio- or chemotherapy) human adult pulmonary tissues. Using double immunofluorescence and avidin biotin complex (ABC) techniques on paraffin sections, presence of CD44s and CD44v isoforms (CD44v4, CD44v6, CD44v9) has been analyzed. In normal lung tissue, CD44s is present at the cell surface of alveolar macrophages, in some interstitial cells and in epithelial cells. It is also present in epithelial and non-epithelial cells during lung development. CD44v isoforms containing exon v6 and v9 encoded epitopes are selectively detectable in normal epithelial cells with a strong basolateral distribution pattern in the entire population of type II pneumocytes and in basal cells of the bronchial epithelium. During development exon v9 encoded isoforms appear at the pseudoglandular stage, whereas CD44v6 has only been found at the saccular stage. Examination of 12 fibrotic lung samples has revealed major alterations in the CD44 expression in comparison to normal lung tissue. These changes include cytoplasmic deposits of CD44s in alveolar epithelial cells and reduced expression of the CD44v6 and CD44v9 isoforms in alveolar epithelial and bronchial epithelial cells. The results suggest that CD44v isoforms may be utilized by type II pneumocytes in epithelial-mesenchymal interactions and in the maintenance of the pulmonary histoarchitecture.(ABSTRACT TRUNCATED AT 250 WORDS)
Am J Respir Cell Mol Biol 1995 Dec
PMID:Distinct expression patterns of CD44 isoforms during human lung development and in pulmonary fibrosis. 757 2

The invariant chain (Ii, CD74) is a transmembrane glycoprotein that is transiently associated with the MHC class II antigens in the endoplasmic reticulum and in endocytic vesicles. An activator of protein kinase C (PKC), 12-O-tetradecanoyl-1,2-phorbol 13-acetate (TPA), was found to enhance expression of Ii mRNA in the murine B lymphoma cell line, A20, 6-48 hr following treatment. In contrast, TPA did not induce the Ii in NIH 3T3 fibroblasts. TPA addition to either cell line activated PKC. Pretreatment of A20 cells with the PKC inhibitors, staurosporine or chelerythrine chloride, for 5 or 20 min prior to addition of TPA, decreased Ii mRNA levels when compared to cells treated with TPA alone. A 20 min preincubation with the highly specific PKC inhibitor, calphostin C, completely blocked the TPA enhanced expression of the Ii suggesting that activation of PKC was responsible for TPA increased Ii mRNA levels. IFN-gamma also blocked the TPA increased Ii mRNA levels. Constitutive expression of Ii mRNA was decreased by treatment with staurosporine but not chelerythrine chloride or calphostin C, suggesting that non-PKC protein kinases may also be important for maintaining high levels of Ii mRNA in these cells. Western blot analysis using PKC isotype specific antibodies showed that A20 cells express PKC delta abundantly whereas NIH 3T3 cells express primarily PKC alpha. These data suggest that a PKC delta mediated signal transduction pathway plays a crucial role in up-regulation of the Ii.
Mol Immunol 1995 Jun
PMID:Invariant chain (CD74) gene regulation: enhanced expression associated with activation of protein kinase C delta in a murine B lymphoma cell line. 764 56

In addition to specific ligand binding elements, receptor assembly for interleukin(IL)-6, oncostatin-M, leukaemia inhibitory factor, ciliary neurotrophic factor and IL-11 includes an additional unit, gp130. This molecule is a transmembrane glycoprotein of 130 kDa. In this paper, reviewing molecular, biochemical and functional data on gp130, we describe the dissimilar action of IL-3 on the expression of the binding unit of the IL-6 receptor and that of gp130. According to FACS studies, resting basophils express only IL-6 receptors and no gp130 molecules on the plasma membranes. After incubation with IL-3, the surface appearance and de novo transcription of gp130 was shown by FACS and mRNA polymerase chain reaction analysis.
J Mol Recognit 1994 Dec
PMID:Separate regulation of a membrane protein, gp130, present in receptor complex specific for interleukin-6 and other functionally related cytokines. 773 54

The sec71-1 and sec72-1 mutations were identified by a genetic assay that monitored membrane protein integration into the endoplasmic reticulum (ER) membrane of the yeast Saccharomyces cerevisiae. The mutations inhibited integration of various chimeric membrane proteins and translocation of a subset of water soluble proteins. In this paper we show that SEC71 encodes the 31.5-kDa transmembrane glycoprotein (p31.5) and SEC72 encodes the 23-kDa protein (p23) of the Sec63p-BiP complex. SEC71 is therefore identical to SEC66 (HSS1), which was previously shown to encode p31.5. DNA sequence analyses reveal that sec71-1 cells contain a nonsense mutation that removes approximately two-thirds of the cytoplasmic C-terminal domain of p31.5. The sec72-1 mutation shifts the reading frame of the gene encoding p23. Unexpectedly, the sec71-1 mutant lacks p31.5 and p23. Neither mutation is lethal, although sec71-1 cells exhibit a growth defect at 37 degrees C. These results show that p31.5 and p23 are important for the trafficking of a subset of proteins to the ER membrane.
Mol Biol Cell 1994 Sep
PMID:Nonlethal sec71-1 and sec72-1 mutations eliminate proteins associated with the Sec63p-BiP complex from S. cerevisiae. 784 22

The nef gene is conserved throughout the primate lentivirus family. Although dispensable in vitro, an important role for nef in vivo is suggested by the failure of SIV nef mutants to establish persistent viraemia. Although the biochemical function of the Nef protein remains equivocal, a consistent theme has emerged with the reproducible observation that Nef expression results in the down-modulation of the cell surface marker CD4. Down-modulation requires amino acid sequences within the cytoplasmic domain of CD4 but occurs by a mechanism distinct from the normal serine phosphorylation-dependent pathway. As CD4 is a transmembrane glycoprotein and Nef a myristoylated protein targeted to the cytoplasmic face of the plasma membrane we considered that a direct interaction between Nef and CD4 might play a role in down-modulation. Here we demonstrate that a baculovirus-expressed Nef-GST fusion protein interacts specifically with CD4. This interaction requires co-expression in the same cell and is dependent on Nef myristoylation. The site of Nef interaction maps to the cytoplasmic domain of CD4, as a deletion mutant lacking this domain fails to interact with Nef. This observation sheds new light on the biochemical function of Nef and offers new opportunities for the future development of HIV chemotherapy.
J Mol Biol 1994 Aug 12
PMID:Myristoylation-dependent binding of HIV-1 Nef to CD4. 805 54

The outer membrane glycoprotein gp120 and the transmembrane glycoprotein gp41 are predominant targets of the humoral immune response to infection by human immunodeficiency virus type 1. The third hypervariable region (V3 loop) is the principal neutralizing domain and is the primary target of neutralizing antibodies directed against the envelope proteins of HIV-1. The V3 loop is also the major determinant for HIV-1 cell-specific tropism. To further characterize the humoral immune response directed against the gp120 envelope proteins, we expressed two prototypic gp120 envelope proteins (LAI/HXB2 and ADA) and chimeric gp120 envelope proteins in stable transfected Drosophila melanogaster Schneider 2 cells. Sera from four infected adults over the course of infection [McNearney et al. (1992) Proc. natn. Acad. Sci. U.S.A. 89, p. 10,242] were assayed for reactivity with the respective envelope proteins. Sera obtained at early stages preferentially recognized the gp120 envelope protein ADA, whereas in later stages of infection the sera showed diminished reactivity with both gp120 LAI/HXB2 and gp120 ADA. Chimeric envelope proteins revealed that the humoral response was directed primarily against the V3 loop of gp120 ADA. Furthermore, 22 sera from HIV-1 infected individuals in different stages of the disease were tested. Reactivity of sera with the gp120 envelope protein ADA was seven-fold higher than with the gp120 envelope protein LAI/HXB2. Our results suggest that the humoral immune response is preferentially elicited against the V3 loop of the prototypic macrophage-tropic gp120 envelope protein ADA.
Mol Immunol 1995 Oct
PMID:Sera from HIV-1 infected individuals in all stages of disease preferentially recognize the V3 loop of the prototypic macrophage-tropic glycoprotein gp120 ADA. 854 53

Yeast Sec12p, a type II transmembrane glycoprotein, is required for formation of transport vesicles from the endoplasmic reticulum (ER). Biochemical and morphological analyses have suggested that Sec12p is localized to the ER by two mechanisms: static retention in the ER and dynamic retrieval from the early region of the Golgi apparatus. The rer1 mutant we isolated in a previous study mislocalizes the authentic Sec12p to the later compartments of the Golgi. To understand the role of RER1 on Sec12p localization, we cloned the gene and determined its reading frame. RER1 encodes a hydrophobic protein of 188 amino acid residues containing four putative membrane spanning domains. The rer1 null mutant is viable. Even in the rer1 disrupted cells, immunofluorescence of Sec12p stains the ER, implying that the retention system is still operating in the mutant. To determine the subcellular localization of Rer1p, an epitope derived from the influenza hemagglutinin was added to the C-terminus of Rer1p and the cells expressing this tagged but functional protein were observed by immunofluorescence microscopy. The anti-HA monoclonal antibody stains the cells in a punctate pattern that is typical for Golgi proteins and clearly distinct from the ER staining. This punctate staining was in fact exaggerated in the sec7 mutant that accumulates the Golgi membranes at the restrictive temperature. Furthermore, double staining of Rer1p and Ypt1p, a GTPase that is known to reside in the Golgi apparatus, showed good colocalization. Subcellular fractionation experiments indicated that the fractionation pattern of Rer1p was similar to that of an early Golgi protein, Och1p. From these results, we suggest that Rer1p functions in the Golgi membrane to return Sec12p that has escaped from the static retention system of the ER.
Mol Biol Cell 1995 Nov
PMID:Membrane protein retrieval from the Golgi apparatus to the endoplasmic reticulum (ER): characterization of the RER1 gene product as a component involved in ER localization of Sec12p. 858 49


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