Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0001511 (Adhesion)
 5,955 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A 22 x 10(3) Mr protein (abbreviated 22K) that copurifies with dermatan sulfate proteoglycans (DS-PGs) following the biochemical fractionation of bovine fetal skin has been evaluated for adhesion-promoting activity in vitro using Balb/c 3T3 cells, as well as bovine and human dermal fibroblasts. Substrata coated with 22K protein promote attachment of a subset of 3T3 and dermal fibroblasts that respond to plasma fibronectin (pFN) substrata. Cells on 22K protein display partial cytoplasmic spreading, comparable to that of cells adhering to cell-binding fragments of pFN. Adhesion activity of 22K is not due to contamination with known adhesive proteins of dermal matrices and is not dermal cell type-specific, since two classes of neuronal cells also respond effectively to 22K substrata. DS-PGs from cartilage or skin completely inhibit 22K adhesion activity when the PGs are adsorbed to 22K substrata under conditions prohibiting PGs from binding to substrata directly. Cartilage chondroitin/keratan sulfate proteoglycan at much higher concentrations is only partially inhibitory. Inhibition by DS-PGs is mediated by DS chains binding to 22K. Properties of the cell surface 'receptor' for 22K protein were tested by several approaches. It is not cell surface DS-PG, since: (1) cells unable to produce this proteoglycan class also responded; (2) cells treated with chondroitinase ABC responded equally well; and (3) substrata of proteoglycan-binding platelet factor-4 generated responses from cells that were quantitatively and qualitatively different. A synthetic peptide in the medium containing the Arg-Gly-Asp-Ser (RGDS) sequence completely inhibited responses to 22K substrata. This observation, coupled with sequencing data of 22K protein revealing an Arg-Gly-Ala-Thr sequence at residues 151-154, suggest that 22K protein mediates adhesion by cell surface integrin binding. Therefore, this newly discovered matrix protein from skin may serve as a communication link between the dermal fibroblast cell surface and its extracellular matrix environment.
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PMID:Extracellular matrix adhesion-promoting activities of a dermatan sulfate proteoglycan-associated protein (22K) from bovine fetal skin. 193 76

Adhesion of the obligate intracellular bacterium Chlamydia trachomatis to host cells is associated with a flux of Ca2+ across the cell membrane, and infection is enhanced by treatment of host cells with Ca2+ ionophore. The possibility that Ca2+ might interact with host cell Ca2+ regulatory proteins to promote chlamydial infection was investigated. Treatment of HeLa 229 cells with the calmodulin inhibitors pimozide, trifluoperazine, chlorpromazine, promethazine or haloperidol reduced chlamydial infectivity as measured by inclusion counting or the specific incorporation of [3H]threonine. The inhibitory effect was reversible, dose-related and shown to be associated with impairment of chlamydial adhesion and uptake by the host cells. This effect was clearly distinguished from the delayed maturation of chlamydiae due to continuous exposure to calmodulin inhibitors which may result from a decrease in the availability of high energy compounds from the host cells necessary for chlamydial growth. The possible mechanisms for calmodulin-mediated chlamydial endocytosis are discussed.
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PMID:Control mechanisms governing the infectivity of Chlamydia trachomatis for HeLa cells: the role of calmodulin. 642 68

We recently described the molecular cloning of a murine cDNA encoding an endothelial cell surface ligand for the leukocyte adhesion molecule, L Selectin (Lasky, L. A., Singer, M., Dowbenko, D., Ima, Y., Henzel, W., Grimley, C., Gennie, C., Gillett, N., Watson, S., and Rosen, S. D (1992) Cell 69, 927-938). This glycoprotein ligand was found to resemble mucins in that it contained a large percentage of serine and threonine residues that were apparently O-glycosylated. At least one of the O-linked carbohydrates found on this endothelial ligand interacts with the lectin domain of L Selectin. These data suggest that this endothelial ligand is an adhesion molecule that accomplishes cell binding by presenting carbohydrate(s) to the lectin domain of L Selectin, and the name GLYCAM 1 (GLY-cosylation-dependent Cell Adhesion Molecule 1) has been proposed. In this paper we describe the genomic structure and chromosomal localization of this unique Selectin ligand. The gene has been found to be encoded on four separate exons, and it thus differs from the cell surface mucin leukosialin, whose coding region is contained on one exon, but is similar to glycophorin and CD34, other cell surface mucins whose genes are divided into multiple coding exons. While there is some correlation between exon division and protein domain structure, these relationships are not as clear as they are in other genes. The gene encoding GLYCAM 1 was found to map to murine chromosome 15.
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PMID:Structure and chromosomal localization of the murine gene encoding GLYCAM 1. A mucin-like endothelial ligand for L selectin. 768 41

Recently we described the isolation of a mouse cDNA clone encoding a mucin-like endothelial glycoprotein that appears to function as an adhesive ligand for L selectin. This ligand has been named GlyCAM 1 (Gly-cosylation-dependent Cell Adhesion Molecule 1) because its adhesive interactions with the L selectin lectin domain require that the GlyCAM 1 polypeptide chain be appropriately modified with carbohydrates. These carbohydrate modifications include the addition of sialic acid as well as sulfate residues to O-linked carbohydrate side chains that are clustered in two serine/threonine-rich domains of the mucin. An additional interesting structure that may have relevance to the association of GlyCAM 1 with the lumenal surface of the endothelium was a potential amphipathic helix at the C terminus of the glycoprotein. In order to examine the importance of the postulated O-linked domains as well as the potential amphipathic helix, we have cloned the rat homologue of GlyCAM 1. The sequence of this clone reveals a serine/threonine-rich protein that is highly homologous with the mouse GlyCAM 1. As was found for the mouse GlyCAM 1, the rat homologue shows a clustering of these potential O-linked carbohydrate acceptors in two domains of the protein. Interestingly, many of the serines and threonines are found to be spaced identically in the two homologues, consistent with the possibility that both density and position of the O-linked side chains may be important for appropriate L selectin-mediated adhesion. In support of its postulated functional importance, the C-terminal potential amphipathic helix is conserved in the rat homologue. Finally, immunoprecipitation analysis of [35S]sulfate-labeled rat lymph nodes with either a mouse L selectin IgG chimera or a peptide antiserum directed against a relatively conserved portion of mouse GlyCAM 1 demonstrates a approximately 45-kDa sulfated ligand in rat lymph nodes that is analogous to that previously described for mouse lymph nodes.
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PMID:Cloning of a rat homologue of mouse GlyCAM 1 reveals conservation of structural domains. 810 Feb 29

Integrins are receptor molecules for extracellular matrix molecules (e.g., the beta(1) family), serum components (alpha(v) family) and immunoglobulin family adhesion molecules (beta(2) family). Integrin-dependent adhesion has also been shown to have metabolic consequences. Adhesion to a variety of extracellular matrix proteins, such as fibronectin, collagen, and laminin, is a potent regulator of cell growth, differentiation, and gene expression. Ligand binding or aggregation of integrin receptors initiates a number of metabolic changes including activation of serine/threonine and tyrosine kinases, increased Ca2+ influx, increased cytoplasmic alkalinization, and altered inositol lipid metabolism. In some instances activation of transcription factors and induction of gene expression have also been demonstrated. Components of key signaling pathways involving integrins are beginning to be identified. Some studies have shown that integrins form multi-component complexes with signal transduction molecules. Elucidating the interactions of the signal transduction molecules with each other and with the integrin cytoplasmic domains will be key to understanding the initial events of signal transduction through the integrins.
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PMID:Integrin-dependent signal transduction. 880 77

We investigated the effects of signaling molecule inhibitors on the expression and function of beta1 integrins in Jurkat cells. Jurkat cells expressed alpha4beta1 and alpha5beta1, with significant levels of constitutively activated beta1 integrins as assessed by labeling with mAb 15/7 that distinguishes between activation states. Adhesion to fibronectin (Fn) was mediated equally through alpha4 and alpha5 subunits, and was potentiated by the beta1 integrin activating mAb 8A2. Fn adhesion was decreased by okadaic acid through effects on both alpha4beta1, and alpha5beta1. Tyrphostin A23 also decreased adhesion but was less potent. Neither inhibitor had any effect on the surface expression of total or activated beta1 integrins. The effect of tyrphostin was completely reversed by 8A2; the effect of okadaic acid was only partially reversed. Using Calyculin A, we determined that Jurkat adhesion to Fn was regulated via protein phosphatase 1, independent of the levels of integrins or integrin activation epitopes. Activation of Jurkat cells with a CD3-stimulating mAb enhanced adhesion to Fn and was partially blocked by okadaic acid. These data demonstrate different regulatory pathways for constitutive versus activation-dependent adhesion via beta1 integrins, and implicate both tyrosine kinases and serine-threonine phosphatases in integrin function.
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PMID:Beta 1 integrin-dependent binding of Jurkat cells to fibronectin is regulated by a serine-threonine phosphatase. 985 Jan 57

Adhesion of tumor cells to host cell layers and subsequent transcellular migration are pivotal steps in cancer invasion and metastasis. The small GTPase Rho controls cell adhesion and motility through reorganization of the actin cytoskeleton and regulation of actomyosin contractility. Cultured rat MM1 hepatoma cells migrate through a mesothelial cell monolayer in vitro in a serum-dependent, Rho-mediated manners. Among several proteins isolated as putative target molecules of Rho, the ROCK (ROK) family of Rho-associated serine-threonine protein kinases are thought to participate in the induction of focal adhesions and stress fibers in cultured cells, and to mediate calcium sensitization of smooth muscle contraction by enhancing phosphorylation of the regulatory light chain of myosin. Transfection of MM1 cells with cDNA encoding a dominant active mutant of ROCK conferred invasive activity independently of serum and Rho. In contrast, expression of a dominant negative, kinase-defective ROCK mutant substantially attenuated the invasive phenotype. A specific ROCK inhibitor (Y-27632) blocked both Rho-mediated activation of actomyosin and invasive activity of these cells. Furthermore, continuous delivery of this inhibitor using osmotic pumps considerably reduced the dissemination of MM1 cells implanted into the peritoneal cavity of syngeneic rats. These results indicate that ROCK plays an essential part in tumor cell invasion, and demonstrate its potential as a therapeutic target for the prevention of cancer invasion and metastasis.
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PMID:An essential part for Rho-associated kinase in the transcellular invasion of tumor cells. 993 Aug 72

Adhesion of fibroblasts to extracellular matrices via integrin receptors is accompanied by extensive cytoskeletal rearrangements and intracellular signaling events. The protein kinase C (PKC) family of serine/threonine kinases has been implicated in several integrin-mediated events including focal adhesion formation, cell spreading, cell migration, and cytoskeletal rearrangements. However, the mechanism by which PKC regulates integrin function is not known. To characterize the role of PKC family kinases in mediating integrin-induced signaling, we monitored the effects of PKC inhibition on fibronectin-induced signaling events in Cos7 cells using pharmacological and genetic approaches. We found that inhibition of classical and novel isoforms of PKC by down-regulation with 12-0-tetradeconoyl-phorbol-13-acetate or overexpression of dominant-negative mutants of PKC significantly reduced extracellular regulated kinase 2 (Erk2) activation by fibronectin receptors in Cos7 cells. Furthermore, overexpression of constitutively active PKCalpha, PKCdelta, or PKCepsilon was sufficient to rescue 12-0-tetradeconoyl-phorbol-13-acetate-mediated down-regulation of Erk2 activation, and all three of these PKC isoforms were activated following adhesion. PKC was required for maximal activation of mitogen-activated kinase kinase 1, Raf-1, and Ras, tyrosine phosphorylation of Shc, and Shc association with Grb2. PKC inhibition does not appear to have a generalized effect on integrin signaling, because it does not block integrin-induced focal adhesion kinase or paxillin tyrosine phosphorylation. These results indicate that PKC activity enhances Erk2 activation in response to fibronectin by stimulating the Erk/mitogen-activated protein kinase pathway at an early step upstream of Shc.
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PMID:Protein kinase C regulates integrin-induced activation of the extracellular regulated kinase pathway upstream of Shc. 1018 52

Adhesion of tumor cells to host cell layers and subsequent migration are pivotal steps in cancer invasion and metastasis. The small GTP-binding protein RhoA controls cell adhesion and motility through organization of the actin cytoskeleton and regulation of actomyosin contractility. Cultured rat MM1 hepatoma cells migrate through a mesothelial cell monolayer in vitro in a serum-dependent, RhoA-mediated manner (K. Yoshioka et al., J. Biol. Chem., 273: 5146-5154, 1998). Furthermore, the ROCK family of RhoA-associated serine-threonine protein kinases is involved in this migration, and an inhibitor for these kinases effectively inhibits the invasion of MM1 cells in vitro and in vivo (K. Itoh et al., Nat. Med., 5: 221-225, 1999). Although there have been no reports of genetic alterations directly affecting RhoA in human cancer, the expression level of RhoA in tumors has been several times higher than that of surrounding normal tissue; RhoA was especially highly expressed in the metastatic region. To determine whether RhoA is activated by its overexpression, we made stable transfectants of MM1 cells expressing various levels of wild-type human RhoA. These transfectants showed promoted invasive ability in vitro in the absence and presence of 1-oleoyl-lysophosphatidic acid, marked adherence to the plastic culture dish with scattered shape, elevated phosphorylation of Mr 20,000 myosin light chain, and translocation of RhoA protein from the cytosol to the membrane. All of these phenotypes were similar to those of active RhoA transfectants, correlated with the expression level of RhoA and reversed by the treatment of the cells with Clostridium botulinum exoenzyme C3 ADP-ribosyltransferase. In addition, overexpression of wild-type RhoA in MM1 cells also conferred invasive ability in vivo after the cells were transplanted into the syngeneic rats. Thus, high expression of RhoA in the cell facilitates the translocation of this protein to the membrane, where it is activated, resulting in the stimulation of the RhoA-ROCK-actomyosin system, leading to invasion.
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PMID:Overexpression of small GTP-binding protein RhoA promotes invasion of tumor cells. 1021 13

Adhesion is associated with tyrosine phosphorylation in many types of cells. Although macrophages are known to adhere and phagocytose foreign particles, the signal transduction pathway of macrophages in response to adhesion to the foreign substrate has not been fully investigated. In the present study we investigated tyrosine-phosphorylated proteins and phosphorylation of paxillin in alveolar macrophages (AMs) following adhesion to a plastic substrate. Adhesion to a plastic dish resulted in tyrosine phosphorylation of a 68 000 MW protein, which was shown, by immunoprecipitation and immunoblotting in the present study, to be a rat Syk kinase. Treatment with erbstatin reduced both tyrosine phosphorylation of Syk and adherence of AMs, while treatment with cytochalasin B inhibited spreading of AMs but did not inhibit tyrosine phosphorylation of Syk. These results suggest that tyrosine phosphorylation of Syk plays an important role in adhesion of AMs to the plastic substrate, but not in AM spreading. Paxillin is known to be tyrosine phosphorylated following adhesion to the extracellular matrix in many types of cells. However, paxillin appeared to be serine/threonine phosphorylated rather than tyrosine phosphorylated following adhesion of AMs to the plastic substrate. Treatment with A23187 (a calcium ionophore), but not phorbol 12-myristate 13-acetate (PMA; a protein kinase C stimulator), induced tyrosine phosphorylation of Syk in non-adherent AMs. Treatment with either A23187 or PMA caused electromobility changes of paxillin that were mainly a result of serine/threonine phosphorylation. These results suggest that adhesion to the plastic substrate leads to two differently regulated events in AMs: tyrosine phosphorylation of Syk and serine/threonine phosphorylation of paxillin, both of which are probably mediated by an increase in intracellular calcium.
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PMID:Syk and paxillin are differentially phosphorylated following adhesion to the plastic substrate in rat alveolar macrophages. 1044 62


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