Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:Q07644 (polypeptide)
 72,197 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We have investigated whether species-specific epitopes of human fibronectin are localized at a specific domain of fibronectin using rabbit polyclonal antibodies. Tryptic fragments of human fibronectin were tested for reactivity with anti-human fibronectin antibody, which had been previously absorbed with other animal fibronectin to establish species specificity. Human-specific epitopes were found to be present on 75,000, 65,000, and 42,000 dalton fragments. The 42,000-dalton fragment shares almost all the epitopes with the 75,000 and 65,000 dalton fragments. It does not promote BHK cell spreading, whereas the 75,000 and 65,000 dalton fragments do. The amino acid sequence from the amino terminus of the 42,000-dalton fragment is Asp/Gly-Gln/Val-?-Ile-Val-, which is almost identical to the sequence Asp-Gln-Cys-Ile-Val- located in the carboxyl terminal 1/3 of the collagen-binding domain of human fibronectin (Kornblihtt et al. (1985) EMBO J. 4, 1755-1759). These results suggest that human fibronectin bears human-specific epitopes mainly on the amino-terminal half of domain 4 (Hayashi & Yamada (1983) J. Biol. Chem. 258, 3332-3340) located between the collagen and cell binding domains almost at the center of the fibronectin polypeptide. The domain specific for human fibronectin may be a general species-specific domain of animal fibronectins.
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PMID:On the origin of species specificity of fibronectin. Immunological identification of a species-specific domain of human fibronectin. 242 6

The amino acid sequence of the vitronectin receptor alpha subunit deduced from cDNA is presented. The sequence defines a 1047-amino-acid polypeptide precursor with a putative signal sequence, a large extracellular domain with several sites homologous to calcium binding sites in other proteins, a transmembrane domain, and a 32-amino-acid cytoplasmic domain. The 7-kilobase vitronectin receptor alpha subunit mRNA was found to be expressed in all cell lines examined, including endothelial cells, K562 and HEL leukemia cells, and osteosarcoma cells. In the two leukemia cell lines, the expression of the vitronectin receptor mRNA, as well as that of the fibronectin receptor, was enhanced in the presence of phorbol ester, a treatment known to increase the adhesiveness of these cells. The HEL cells were the only ones among the cell lines tested that also contained the mRNA of the platelet adhesion receptor alpha subunit, glycoprotein IIb. The expression of glycoprotein IIb was slightly enhanced by treatment of the cells with phorbol ester. These results complete the partial cDNA sequence of the vitronectin receptor alpha subunit published previously (Suzuki, S., Argraves, W. S., Pytela, R., Arai, H., Krusius, T., Pierschbacher, M. D., and Ruoslahti, E. (1986) Proc. Natl. Acad. Sci. U.S.A., 83, 8614-8618), confirm that the vitronectin receptor, and not IIb, is expressed in endothelial cells, and show that changes in the level of its expression correlate with changes in cell adhesiveness.
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PMID:Amino acid sequence of the vitronectin receptor alpha subunit and comparative expression of adhesion receptor mRNAs. 244

A series of 20 cases of pleomorphic adenoma and 19 cases of adenoid-cystic carcinoma of the salivary glands, and one case in the mammary location, were investigated regarding immunohistochemical reactivity for Tissue Polypeptide Antigen (TPA), Pre-Keratins, Vimentin, S-100 Protein, and their arrangement pattern of fibronectin. As a whole, the results support the hypothesis of morpho-structural and mainly, onto-histogenetic similarities between these tumours, but they also underline the need for great care in outlining their morpho-functional features, in relation to their different prognoses.
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PMID:Pleomorphic adenoma and adenoid-cystic carcinoma of the salivary glands: comparative immunohistochemical patterns. 244 99

The avian 140-KD cell adhesion receptor or "integrin," a complex of three glycoproteins with molecular masses averaging 140 KD, interacts with extracellular fibronectin and forms a linkage complex that co-localizes with intracellular actin. To probe the molecular interactions involved in this linkage complex, we used monoclonal antibodies and a combination of immunolocalization approaches to determine whether any component was transmembrane. Immunoadsorption and immunoblotting experiments demonstrated that anti-120-KD Mabs recognized the band 3 component of integrin isolated from chicken embryo fibroblasts (CEF) by JG22E immunoaffinity chromatography, and they co-localize with anti-fibronectin and polyclonal anti-integrin at cell contact sites in double-labeling experiments. Immunofluorescence experiments involved comparisons of double-labeled intact cells or substrate-attached, ventral plasma membrane "rip-off" fragments, using anti-fibronectin and each of the anti-120-KD Mabs. The extracellular faces of living intact cells were strongly labeled by a majority (approximately 70%) of the anti-120-KD Mabs at fibronectin-membrane attachment sites. The remainder (approximately 30%) labeled intact cells weakly or not at all. However, although the anti-120-KD Mab ES186 did not stain living cells, it did demonstrate positive staining above substratum contact sites over entire isolated rip-off membranes. In contrast, Mabs directed against putative extracellular epitopes and anti-fibronectin antibodies did not label these sites at the center of rip-offs unless the membranes were detergent permeabilized. Proteolysis experiments suggested that the ES186 epitope was located at one end of the molecule, since removal of short fragments from integrin band 3 concomitantly removed or destroyed the ES186 epitope, whereas the extracellular epitopes still remained. These experiments directly demonstrate that integrin band 3 is a transmembrane polypeptide with at least one epitope recognized by anti-120-KD Mabs on the cytoplasmic side of the plasma membrane and at least one epitope on the extracellular cell surface.
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PMID:Transmembrane orientation of the fibronectin receptor complex (integrin) demonstrated directly by a combination of immunocytochemical approaches. 244 91

Cytotactin is an extracellular glycoprotein that influences neuron-glia interactions. It has been shown to appear in multiple forms that are differentially expressed in neural and non-neural tissues during vertebrate development. We report here the isolation and characterization of a cytotactin cDNA clone (lambda C801) that encodes 933 amino acids, equivalent to about half of a cytotactin polypeptide. Clone lambda C801 is an authentic cytotactin cDNA: it encodes a polypeptide that reacts with a monoclonal anti-cytotactin antibody and its deduced amino acid sequence is identical for 15 amino acids to the directly determined sequence of a CNBr fragment that reacted with the same antibody. Southern blot analyses with fragments of lambda C801 suggested that there may be only one cytotactin gene, but RNA transfer blots detected multiple mRNAs ranging in size from 6.5 to 8.0 kilobases. An 8.0-kilobase message and a Mr 240,000 cytotactin polypeptide were present in embryonic gizzard but not brain, while a 7.2-kilobase message and a Mr 220,000 polypeptide were present in brain but not gizzard. These results indicate that differential splicing of primary transcripts of the cytotactin gene yields various site-specific polypeptides. Sequence analyses of lambda C801 indicated that it specifies a region with extensive similarities to other proteins: the sequence begins with four consecutive epidermal growth factor-like repeats that are followed by eight segments that closely resemble each other and the type III repeats in fibronectin, and it ends with a 66 amino acid sequence similar to part of the beta and gamma chains of fibrinogen. One fibronectin-like repeat contains a single Arg-Gly-Asp sequence. The similarities with all three of these apparently unrelated proteins are extensive, suggesting that cytotactin has an evolutionary and possibly a functional relationship to each.
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PMID:A cDNA clone for cytotactin contains sequences similar to epidermal growth factor-like repeats and segments of fibronectin and fibrinogen. 245 Dec 43

Platelet membrane glycoprotein (GP) IIb-IIIa is a component of a receptor for the adhesive proteins fibrinogen, fibronectin, and von Willebrand factor. GPIIb is initially synthesized as a single-chain polypeptide that is proteolytically processed to yield the two chains of mature GPIIb present on the cell surface. Analysis of the amino acid sequence surrounding the proposed light-heavy chain junction of GPIIb suggests a second potential site following a pair of basic residues 12-15 residues upstream from the reported amino terminus of the light chain. We have utilized anti-peptide antibodies to examine the possibility of alternative cleavage at these two potential sites. Peptide V43 precedes the dibasic sequence and is known to reside in the heavy chain. Peptide V41 contains the sequence between the two potential sites. In immunoblots, anti-V43 reacted only with the heavy chain while anti-V41 reacted only with the light chain. Immunoprecipitation of surface-labeled platelets indicated 97% of the GPIIb light chain contains the V41 sequence while approximately 3% of GPIIb molecules lack the V41 sequence on both the light and heavy chains. These data indicate that GPIIb is primarily cleaved 12-15 amino acids upstream from the reported amino terminus of the light chain while in a minor proportion of GPIIb molecules cleavage occurs at both sites.
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PMID:Alternative proteolytic processing of platelet membrane glycoprotein IIb. 245 17

Normal human epidermal keratinocytes (KC) grown under conditions that maintain the undifferentiated state are highly motile. Migration of these cells as measured in two different assays (migration out of an agarose drop explant, and into micropore filters in a modified Boyden chamber), is stimulated by fibronectin (FN) and to a lesser extent by thrombospondin (TSP). In contrast, laminin (LN) inhibits KC migration. Cultivation of the cells for 1 day under conditions that induce differentiation (ie, in the presence of 1.4 mM Ca2+) suppresses KC motility. A number of soluble growth modulating polypeptide factors also influence KC migration. Transforming growth factor-beta (TGF-beta) and epidermal growth factor (EGF) stimulate KC motility. These factors simultaneously induce KC production of FN and a significant portion of the stimulated motility can be inhibited with antibodies to FN. EGF and somatomedin-C (SM-C), but not TGF-beta, also stimulate TSP production while EGF and SM-C (but not TGF-beta) induce KC proliferation. In contrast to these factors, interferon-gamma (INF-gamma) inhibits KC production of both FN and TSP and concomitantly inhibits both motility and proliferation. These data suggest that KC properties essential for normal wound healing (ie, motility and proliferation) are regulated by both extracellular matrix molecules and soluble peptide factors. Finally, these effects of various growth promoting and antiproliferative factors on KCs may, in part, be mediated through alteration in the endogenous production of extracellular matrix molecules by KCs.
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PMID:Modulation of keratinocyte motility. Correlation with production of extracellular matrix molecules in response to growth promoting and antiproliferative factors. 245 44

A combination of cDNA sequencing of the complete coding region, protein comparisons, binding site mapping, and electron microscopic imaging has permitted the formulation of a structural model of cytotactin. Cytotactin is a large extracellular matrix glycoprotein that displays a restricted tissue distribution during development. Although there appears to be a single cytotactin gene, multiple cytotactin polypeptides and mRNAs are detected in a variety of tissues. We report here the sequences and relationships of cDNAs that encode the complete amino acid sequences of two cytotactin polypeptides in chicken brain. The translated cDNA sequences agree with those obtained by direct analysis of cytotactin and fragments of the molecule. All regions of the polypeptides appear to be identical except for a 273 amino acid segment found in the larger but not in the smaller. At their amino termini, both polypeptides contain a cysteine-rich segment that probably includes those residues that link monomers into hexamers. This segment is followed by 13 epidermal growth factor-like (EGFL) repeats and then 8 consecutive segments that each resemble the type III repeats found in fibronectin. At their carboxyl termini, the polypeptides are similar to the beta and gamma chains of fibrinogen, including a calcium-binding segment. The additional sequence in the large polypeptide is inserted after the fifth type III repeat and includes three additional type III repeats. On RNA transfer blot analyses, cytotactin cDNA probes detected a 6.4-kilobase (kb) component in both brain and gizzard and larger mRNAs in both tissues, but those in gizzard were larger by about 1 kb than those in brain. A probe specific to the insert did not hybridize to the 6.4-kb mRNA in either tissue but detected the larger mRNAs in both tissues. At least a portion of the insert is thus present in both tissues, but there may be additional inserts in the gizzard mRNAs. The proposed model of cytotactin specifies the orientation of the polypeptides, the localization of interchain disulfide bonds, the structural elements constituting the thin and thick segments (EGFL repeats and type III repeats, respectively), the terminal fibrinogen-like nodular region, and the relative location of the cell-binding region.
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PMID:A detailed structural model of cytotactin: protein homologies, alternative RNA splicing, and binding regions. 246 92

The healing of penetrating nonperforating linear corneal incisions in rabbit was analysed immunohistochemically. Regeneration of the basement membrane (BM) zone was evaluated by analysing the following components using monoclonal antibodies (MAbs): 1) an antigen designated AgHEBM1 (a 66k Mr polypeptide), 2) type VII collagen which is associated with anchoring fibrils and 3) an antigen designated Ag63/D7 which is associated with the lamina densa and anchoring plaques. Concomitant activity in the regenerating stroma was evaluated by analysing the distribution of 1) fibronectin, 2) keratan sulfate and 3) a fetal antigen, designated AgM12, (an intermediate filament associated protein with a Mr of 130k). Synthesis of the BM zone components was not evident at day 2 postwounding but was seen at day 7, only at the deepest aspects of the wounds. Re-establishment of a continuous BM zone was evident by day 60. The stromal regeneration had started by day 7, at the deepest aspect of the wounds, as judged from the distribution of stromal antigens including the fetal antigen AgM12. The number of activated cells (cells expressing AgM12) had decreased significantly by day 30 and diminished by day 60. Between day 30 and day 180 the thickness of the regenerated tissues had not increased significantly although the stroma had not yet reached its normal thickness. Even after six months, the epithelial plug persisted and the concentration of the sulfated epitopes of keratan sulfates in the regenerated stromal matrix were less than in the surrounding nonwounded regions. The cessation of expression of AgM12, by the cells in regenerating stroma, coincided with the relative decrease in extracellular matrix syntheses. The return of the stromal cells to the quiescent state also coincided with re-establishment of a continuous BM zone between the epithelium and the stroma in the regenerated tissue. These observations suggested that the synthesis, assembly and remodeling of stromal and epithelial extracellular matrices during the healing of penetrating corneal wounds may be influenced by the interactions between activated stromal cells and epithelial cells.
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PMID:Unique parameters in the healing of linear partial thickness penetrating corneal incisions in rabbit: immunohistochemical evaluation. 246 54

Anti-cell adhesive activity was examined by the synthetic polypeptide, containing repetitive Arg-Gly-Asp sequence of cell attachment site from fibronectin, poly (Arg-Gly-Asp). The attachment of tumour cells to fibronectin substrate was specifically inhibited by adding poly (Arg-Gly-Asp) in cell surface receptor-mediated and divalent cation-dependent manners, but not by unrelated peptides. In our previous study, the lung metastatic formation of tumour cells was dramatically reduced by intravenous co-injection of anti-cell adhesive poly (Arg-Gly-Asp) with B16-BL6 melanoma cells. These findings suggest that polypeptide-mediated inhibition of pulmonary metastasis is partly due to interference with tumour cell adhesion to the substrates including fibronectin in target organs or tissues.
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PMID:Inhibition of tumour cell adhesion by anti-metastatic polypeptide containing a repetitive Arg-Gly-Asp sequence. 248 85


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