UMLS:C0001511 - FACTA Search

Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Target Concepts:

Query: UMLS:C0001511 (Adhesion)
5,955 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The alternatively spliced type III connecting segment (IIICS) region of fibronectin contains two distinct sites that support the adhesion of melanoma cells. These sites are contained within the synthetic peptides CS1 and CS5 (residues 1-25 and 90-109 of the IIICS, respectively). Recently, the cellular receptor for the CS1 site has been identified as the integrin heterodimer alpha 4 beta 1. In this report, we have investigated the role of the CS5 sequence in melanoma cell adhesion and the identity of its receptor. Adhesion to CS5, when presented to cells as an immobilized IgG conjugate, was blocked by antifunctional monoclonal antibodies directed against either the alpha 4 or beta 1 integrin subunits, but not by antibodies against other subunits, implying that alpha 4 beta 1 is also the receptor for CS5. In peptide inhibition experiments, CS5 was inhibitory for melanoma cell spreading on both CS5-IgG and CS1-IgG conjugates; conversely, CS1 inhibited spreading on both CS1-IgG and CS5-IgG. In both cases, peptide inhibition could be outcompeted by increasing the concentration of substrate-bound conjugate. These results suggest that CS1 and CS5 are recognized by the same or overlapping sites on alpha 4 beta 1. The minimal active sequence within CS5, the tetrapeptide Arg-Glu-Asp-Val (REDV), is somewhat related to the Arg-Gly-Asp-Ser (RGDS) sequence that represents a major active site in the central cell-binding domain (CCBD) of fibronectin. When RGDS peptide homologues were tested for their ability to inhibit spreading of melanoma cells on CS1- and CS5-IgG conjugates, GRGDS, GRGES, and REDV were found to be inhibitory, while GRDGS had no effect. In contrast, spreading on a fibronectin fragment containing the CCBD was inhibited by GRGDS only. GRGDS was also able to elute alpha 4 beta 1 specifically from a CS1 affinity column, confirming directly that alpha 4 beta 1-IIICS interactions are sensitive to peptides containing this recognition motif. Because the minimal active sequence within CS1 is the tripeptide Leu-Asp-Val (LDV; Komoriya et al., manuscript submitted for publication), these findings together define a new adhesive recognition sequence, X-Asp-Y, used by alpha 4 beta 1 for binding to fibronectin. The central aspartate residue in this tripeptide is almost always essential, but some flexibility in the amino acid residues at X (glycine, leucine, or glutamic acid) and Y (serine or valine) is tolerated. Potential models for the interaction of the IIICS region with alpha 4 beta 1 are discussed.
...
PMID:The CS5 peptide is a second site in the IIICS region of fibronectin recognized by the integrin alpha 4 beta 1. Inhibition of alpha 4 beta 1 function by RGD peptide homologues. 175 Sep 29

EDa (EIIIA) is one of two alternatively spliced type III repeats in cellular fibronectin (cFN) lacking in plasma fibronectin (pFN). Previous studies using proteolytic fragments of cFN suggested that EDa may harbor adhesion activity for various Balb/c 3T3 cell derivatives. This putative adhesion activity has now been analyzed more directly. EDa and neighboring type III repeats III11 and III12 from human cFN cDNA were subcloned in various permutations and recombinant minigenes expressed in Escherichia coli. Purified recombinant polypeptide corresponding to EDa type III repeat alone is capable of promoting 3T3 cell attachment and limited cytoplasmic spreading, as are neighboring repeats III11 and III12 when tested as single repeats. While EDa alone exhibited 40-60% of the attachment activity of human pFN depending upon cell type, EDa with both neighboring repeats displayed 70-90% of pFN activity; furthermore, cell spreading was more extensive with the three-repeat molecule. Two experimental approaches indicated that cell surface proteoglycans do not participate in these adhesion processes. Finally, the effects of various oncogenes upon transformation of Balb/c 3T3 cells were investigated. Adhesion activity to all three repeats is completely abrogated by two different ras oncogenes, unaffected by the sis oncogene, and elevated by the src oncogene. Furthermore, ras- revertants of ras-transformed cells had reacquired adhesion activity for EDa and its neighboring repeats. Comparison of individual repeats confirmed oncogene-dependent regulation of receptor activity to these sequences--for 3T3 cells, EDa > III11 = III12, but for src-transformed cells III12 >> EDa > III11. These studies reveal a new adhesion-promoting activity in alternatively spliced EDa and in neighboring repeats III11 and III12; this receptor activity is regulated either positively or negatively subsequent to transformation by specific oncogenes.
...
PMID:Adhesion activity in fibronectin's alternatively spliced domain EDa (EIIIA) and its neighboring type III repeats: oncogene-dependent regulation. 802 May 97

Adhesion functions of cellular fibronectin's (FN) alternatively spliced EDb (EIIIB) domain, as well as its neighboring type III repeats III7 and III8, were investigated with several cultured murine and human cell types. Minigene constructs encoding various permutations of these repeats and expressed in bacteria were used as shown previously in function studies of EDa and its neighboring repeats (P.Xia and L. A. Culp Exp. Cell Res. 213, 253-265, 1994). When substrata of recombinant proteins were incubated with several fibroblastic or neuronal derivative cell lines, cell attachment responses varied widely in a cell-type-specific manner. Balb/c 3T3 cells were shown to adhere to recombinant protein substrata in dose-dependent and EDTA-sensitive manners. Responses also varied with which repeat combinations were being tested, from excellent (Balb/c 3T3, src-3T3), to intermediate (Platt cells), to poor (LZEJ, VA-13, and F11), with EDb plus-containing proteins generally giving better adhesion than EDb minus proteins. On select recombinant proteins, cells showed limited cytoplasmic spreading (3T3 and src-3T3) or neurite extension (Platt and F11), while other cell lines (VA-13 and LZEJ) did not show any morphological changes beyond attachment. Again, EDb plus-containing recombinants were more effective at inducing these morphological changes than the neighboring repeats. These results demonstrate that the EDb domain of cellular FNs and its neighboring type III homology repeats contain important adhesion-promoting sequences, which may be regulated by cells through alternative splicing of FN's primary transcript.
...
PMID:Adhesion mediated by fibronectin's alternatively spliced EDb (EIIIB) and its neighboring type III repeats. 863 99

The extracellular matrix protein tenascin-C is a multidomain protein that regulates cell adhesion. We used two different smooth muscle cell subtypes derived from adult and newborn rat aorta to investigate the interaction of tenascin-C or its various domains with these cells using an adhesion assay. Newborn cells were three times more adherent to tenascin-C than adult cells. Tenascin C-adhering cells remained round, whereas they spread rapidly on a fibronectin substrate. Adhesion assays showed the interaction between tenascin-C and newborn cells to be predominantly RGD-independent. Mg2+ increased newborn cell adhesion to tenascin-C in a concentration-dependent manner, whereas Ca2+ had no effect. To analyze the structure-function relationships of different domains of tenascin-C, we used recombinant full-length fibronectin-like and fibrinogen-like domains and various subdomains corresponding to the alternatively spliced regions of tenascin-C. The cells adhered to the fibrinogen-like domain but not to the fibronectin-like domain or its subdomains. As with the intact tenascin-C molecule, adherent cells remained round, and the Mg2+, but not Ca2+, promoted this interaction. The interaction of cells with the fibrinogen-like region was further mapped to a 30-amino acid peptide located near the carboxyl-terminal part of the tenascin-C molecule. The same 30-amino acid peptide was active in promoting cell migration. Our results provide a basis for understanding the mechanism of interaction of tenascin-C with smooth muscle cells and a framework for isolating membrane binding sites that mediate the cellular responses to this molecule.
...
PMID:Aortic smooth muscle cells interact with tenascin-C through its fibrinogen-like domain. 940 55

The integrin beta5 subunit has only been found to form a heterodimer with subunit alphav which acts as a vitronectin receptor. Integrin alphavbeta5 has been implicated in cell migration and growth factor-induced angiogenesis. In the present study, a mouse liver cDNA library was screened using a human beta5 cDNA fragment obtained by reverse transcriptase PCR (RT-PCR). Three of the clones (MB5, MB15 and MB17) overlapped to give an open reading frame, called beta5A, which is homologous to the human beta5 subunit. The sequence of another clone (MB26), called beta5B, was identical with beta5A, except for a deletion of 29 bp near the 3' end of the open reading frame. The 29 bp deletion resulted in an open-reading-frame shift and a completely different C-terminal sequence in beta5B. beta5A and beta5B were shown, by RT-PCR, to be co-expressed in most mouse tissues tested, although beta5B mRNA was detected at much lower levels than beta5A. beta5A and beta5B mRNAs were also detected in the mouse monocytic cell line, J774, and in isolated mouse peritoneal macrophages. Adhesion of peritoneal macrophages has been shown to up-regulate the expression of both beta5A and beta5B mRNAs. The 29 bp sequence begins with a putative intron-splicing donor site (GTGAT...). A 3' fragment of the mouse integrin beta5 gene was cloned by PCR and sequenced showing that the 29 bp sequence was also immediately followed by an intron. Therefore, the 29 bp sequence was apparently expressed as part of the beta5A mRNA but was spliced out as part of the downstream intron in beta5B. Since the cytoplasmic domains of the integrin beta subunits are important in cytoskeleton attachment and signalling, the two alternatively spliced beta5 isoforms may have distinct roles in cell adhesion and other cellular functions.
...
PMID:cDNA cloning reveals two mouse beta5 integrin transcripts distinct in cytoplasmic domains as a result of alternative splicing. 953 7

CD97 is a newly identified, activation-associated human leucocyte antigen with seven putative transmembrane domains. It has an extended extracellular segment containing several adhesion molecule structure motifs, and has been shown to interact with the human complement regulator, decay-accelerating factor (DAF, CD55). To understand further the interaction between CD97 and DAF, as well as the structure and function of CD97 in general, we have cloned the mouse CD97 cDNA and studied the encoded protein for its membrane association property and ability to interact specifically with the murine decay-accelerating factor. The full-length mouse CD97 cDNA that we have cloned and characterized encodes a protein that is 60% identical to the three epidermal growth factor (EGF) domain-containing form of human CD97 but does not contain the Arg-Gly-Asp (RGD) motif which is present in human CD97. Two other alternatively spliced forms of mouse CD97 were also identified. These forms differ by the number of EGF-like sequence repeats present in the N-terminal region. Northern blot analysis revealed that CD97 is expressed widely in mouse tissues and in resting as well as activated cultured mouse splenocytes. Transient transfection of human embryonic kidney (HEK) 293 cells with the mouse CD97 cDNA in a green-fluorescence protein vector (pEGFP-N1) showed plasma membrane targeting of the expressed protein. Western blot analysis confirmed its membrane association and identified the existence of a processed C-terminal fragment, supporting the notion that CD97 on the cell membrane is composed of post-translationally generated subunits. Adhesion studies demonstrated that normal, but not DAF knockout mouse erythrocytes and splenocytes adhered to mouse CD97-transfected HEK cells. The interaction of CD97 and DAF was found to be species-restrictive in that human erythrocytes were unable to bind to mouse CD97-transfected HEK cells. These results indicate that the general structure, membrane association property and DAF-binding ability of CD97 are conserved and that the adhesive interaction between CD97 and DAF is independent of the RGD motif. The finding that CD97 is distributed widely among various mouse tissues suggests that CD97 may have other roles beyond lymphocyte activation.
...
PMID:Structural characterization of mouse CD97 and study of its specific interaction with the murine decay-accelerating factor (DAF, CD55). 1054 Feb 31

Fibronectin specifically binds to U937 cells (monocytic cell line) in a dose-dependent manner. The specific receptors for the RGD sequence have been identified as alphainfinity 5beta infinity 1wedge alpha infinity: IIb& beta infinity 3, and that for CS1 has been defined as alpha infinity 4& beta infinity 1. RGDS, CS1 peptide, and two peptides together showed similar inhibitory activities on this adhesion, while the 29-kD dispase-digested fragment of the C-terminal heparin-binding domain did not. Thus, the adhesion of fibronectin to U937 cells is mainly mediated by RGDS in the cell-binding domain and CS1 in the alternatively spliced region. Flow cytometry using monoclonal antibodies revealed expressions of alpha infinity 3& beta 1 infinity, alpha4 & beta infinity 1, and alpha infinity 5 beta 1, and not expression of alpha infinity 2 beta infinity 1. Adhesion of U937 cells to fibronectin-coated wells is specific and is inhibited by anti-alpha infinity 4 beta infinity 1 and anti- alpha infinity 5 beta infinity 1 monoclonal antibodies. The IC-50 for anti-alpha infinity 5 beta infinity 1 antibody was almost a log lower than the value for anti-alpha infinity 4 beta infinity 1 antibody. These results demonstrated that interactions of RGDS and CS1 sequence of fibronectin with alpha infinity 5 beta infinity 1 and alpha infinity 4 beta infinity 1& on U937 cells were required for the adhesion of U937 cells to fibronectin. These results may provide further information to understand the mechanism(s) of tumor cell adhesion and atherogenesis.
...
PMID:Human Plasma Fibronectin Mediates Adhesion of U937 Cells by RGD and CS1. 1076 7

The extracellular domain of receptor protein tyrosine phosphatase beta (RPTPbeta) is composed of several domains which mediate its interactions with distinct ligands present on the surface of either neurons or glial cells. Here, we demonstrate that the fibronectin type III domain (FNIII) of RPTPbeta binds to glial tumor-derived cell lines and primary astrocytes. We used affinity purification to isolate several proteins that specifically bind to the FNIII domain of RPTPbeta. One of these, a 240 kDa protein that was purified from U118MG glioblastoma cell, was identified as tenascin C based on the amino acid sequence of several tryptic peptides. The interaction of RPTPbeta with tenascin C was found to mediate cell adhesion. Adhesion and spreading of SF763T astrocytoma cells expressing RPTPbeta on tenascin C was specifically abolished by the addition of a soluble fragment containing the FNIII domain of the receptor. RPTPbeta-dependent cell adhesion was mediated by binding to the alternatively spliced FNIII repeats A1,2,4 (TnfnA1,2,4) of tenascin C. Furthermore, COS cells expressing RPTPbeta adhere to TnfnA1,2,4, while the parental cells did not. These results demonstrate that the FNIII domain of RPTPbeta binds to tenascin C and suggest that RPTPbeta present on glial tumor cells is a primary adhesion receptor system to the extracellular matrix.
...
PMID:Glial tumor cell adhesion is mediated by binding of the FNIII domain of receptor protein tyrosine phosphatase beta (RPTPbeta) to tenascin C. 1131 93

Platelet/Endothelial Cell Adhesion Molecule-1 (PECAM-1 or CD31) is thought to be a vascular-specific protein, but its function has not been clearly defined. Here, we demonstrate by using confocal immunofluorescence microscopy that PECAM-1 is first detected in the mouse blastocyst, which contains no vascular cells, and its expression is restricted to the pluripotent inner cell mass (ICM) cells. Expression is localized to cell-cell borders of the ICM and is detected at the very first signs of blastocoel formation. Consistent with these observations is that embryonic transcripts of PECAM-1 mRNA, as detected by RT-PCR, greatly increase during the morula-to-blastocyst transition and seven of the eight known alternatively spliced isoforms of PECAM-1 are expressed in the blastocyst. The synthesis of PECAM-1 is independent of compaction, cytokinesis, and DNA replication, as it is detected in embryos that are chronologically at the blastocyst stage following culture of 8-cell embryos in Ca2+-free medium, or medium containing cytochalasin D or aphidicolin, respectively. By the late blastocyst stage, PECAM-1 expression is restricted to the pluripotent epiblast, at which point it has a mutually exclusive expression pattern to that of type IV collagen, a basement membrane marker. The reduction in PECAM-1 transcripts in retinoic acid-induced differentiation of F9 teratocarcinoma cells, a model of epiblast-to-primitive endoderm differentiation, confirmed the epiblast-specific expression of PECAM-1. By the egg cylinder stage of development, at which point the epiblast is no longer pluripotent, PECAM-1 is not detected. This ICM-specific pattern of expression suggests a novel developmental role of PECAM-1 that is independent of its function in vascular ontogeny.
...
PMID:Inner cell mass-specific expression of a cell adhesion molecule (PECAM-1/CD31) in the mouse blastocyst. 1139 2

Vascular cell adhesion molecule 1 (VCAM-1, CD106) is expressed as a type I transmembrane integrin counter-receptor on activated endothelium and mediates white blood cell attachment. The alternatively spliced 7-domain (7d) form of VCAM-1 contains a potential thrombin cleavage site. Thrombin proteolysis of 7d-VCAM-1 may help regulate adhesive activity ofVCAM-1. We determined whether 7d-VCAM-1 is proteolyzed and rendered inactive by thrombin. Recombinant extracellular domain of 7d-VCAM-1 was cleaved by thrombin to generate 33- and 44-kDa products. Cleavage was in the sequence PGPR/IAAQIG near the N-terminal border of the alternatively spliced fourth immunoglobulin (Ig)-like module. There was no cleavage of 6d-VCAM-1 lacking the fourth module. Expression of full-length 7d-VCAM-1 presented on Chinese hamster ovary (CHO) monolayers, as detected by flow cytometry with an antibody directed to Ig-like modules 1-3, was reduced by thrombin treatment whereas there was no reduction in the expression of full-length 6d-VCAM-1. Adhesion of blood eosinophils to full-length 7d-VCAM-1 was reduced after treatment of CHO cells with thrombin, whereas adhesion to full-length 6d-VCAM-1 was not affected. We conclude that cleavage of 7d-VCAM-1 by thrombin is a potential mechanism for differential regulation of VCAM-1 splice forms in white blood cell adhesion and trafficking.
...
PMID:Cleavage of human 7-domain VCAM-1 (CD106) by thrombin. 1667 80

1 2 Next >>