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)

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.
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PMID:Structural characterization of mouse CD97 and study of its specific interaction with the murine decay-accelerating factor (DAF, CD55). 1054 Feb 31

The integrin alpha(9)beta(1) mediates cell adhesion to tenascin-C and VCAM-1 by binding to sequences distinct from the common integrin-recognition sequence, arginine-glycine-aspartic acid (RGD). A thrombin-cleaved NH(2)-terminal fragment of osteopontin containing the RGD sequence has recently been shown to also be a ligand for alpha(9)beta(1). In this report, we used site-directed mutagenesis and synthetic peptides to identify the alpha(9)beta(1) recognition sequence in osteopontin. alpha(9)-transfected SW480, Chinese hamster ovary, and L-cells adhered to a recombinant NH(2)-terminal osteopontin fragment in which the RGD site was mutated to RAA (nOPN-RAA). Adhesion was completely inhibited by anti-alpha(9) monoclonal antibody Y9A2, indicating the presence of a non-RGD alpha(9)beta(1) recognition sequence within this fragment. Alanine substitution mutagenesis of 13 additional conserved negatively charged amino acid residues in this fragment had no effect on alpha(9)beta(1)-mediated adhesion, but adhesion was dramatically inhibited by either alanine substitution or deletion of tyrosine 165. A synthetic peptide, SVVYGLR, corresponding to the sequence surrounding Tyr(165), blocked alpha(9)beta(1)-mediated adhesion to nOPN-RAA and exposed a ligand-binding-dependent epitope on the integrin beta(1) subunit on alpha(9)-transfected, but not on mock-transfected cells. These results demonstrate that the linear sequence SVVYGLR directly binds to alpha(9)beta(1) and is responsible for alpha(9)beta(1)-mediated cell adhesion to the NH(2)-terminal fragment of osteopontin.
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PMID:The integrin alpha(9)beta(1) binds to a novel recognition sequence (SVVYGLR) in the thrombin-cleaved amino-terminal fragment of osteopontin. 1059 24

Adhesion-mediated migration is required in a number of physiological and pathological processes. A further quantitative understanding of the relationship between cell migration and cell-substratum adhesiveness may aid in therapeutic or tissue engineering applications. The aim of this work was to quantify three-dimensional cell migration as a function of increasing cell-substratum adhesiveness within reconstituted collagen gels. Cell-substratum adhesiveness was controlled by grafting additional adhesive peptides containing the well-characterized arginine-glycine-aspartic acid sequence to collagen. The three-dimensional migration of multiple individual cells was tracked in real time in an automated fashion for extended periods. Cell displacements were statistically analyzed and fit to a correlated persistent random walk model to estimate root-mean-square speed, directional persistence time, and random motility coefficient. Based on model parameter estimates, cell speed was found to be a monotonically decreasing function of increasing substratum adhesiveness, while the directional persistence time and random motility coefficient exhibited a biphasic dependence, with maximum values at approximately intermediate concentrations of grafted adhesive peptide and hence intermediate cell-substratum adhesiveness. In conclusion, these studies suggest an optimal adhesiveness for three-dimensional random migration, consistent with previous studies on two-dimensional surfaces. However, the maximum in random motility corresponded to a maximum in directional persistence, not in cell speed.
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PMID:Quantitative analysis of adhesion-mediated cell migration in three-dimensional gels of RGD-grafted collagen. 1064 94

The extracellular matrix protein osteopontin (OPN) interacts with a number of integrins, namely alphavbeta1, alphavbeta3, alphavbeta5, alpha9beta1, alpha8beta1, and alpha4beta1. We have investigated the interaction of alpha5beta1 integrin with OPN using K562 cells, which only express alpha5beta1. alpha5beta1 is in a low activation state in this cell line, but can be stimulated to a higher activation state by the phorbol ester TPA. Treating K562 wild-type cells (K562-WT) with TPA stimulated an interaction between alpha5beta1 and OPN. No interaction was seen in the absence of TPA. alpha5beta1 selectively interacted with a GST fusion protein of the N-terminal fragment of OPN (aa17-168), which is generated in vivo by thrombin cleavage of OPN. Expression of the alpha4 integrin in K562 cells (K562-alpha4beta1) stimulated alpha5beta1-dependent binding to aa17-168 in the absence of TPA, suggesting that alpha4beta1 activates alpha5beta1 in K562 cells. Adhesion via alpha5beta1 is mediated by the Arg-Gly-Asp (RGD) motif of OPN, as mutating this sequence to Arg-Ala-Asp (RAD) blocked binding of both cell types. These data demonstrate that thrombin cleavage regulates the adhesive properties of OPN and that alpha5beta1 integrin can interact with thrombin-cleaved osteopontin when in a high activation state.
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PMID:A regulated interaction between alpha5beta1 integrin and osteopontin. 1067 66

Adhesion responses triggered by integrin-class matrix receptors have been implicated in the synaptic reorganization events necessary for certain types of neuronal plasticity. Hippocampal slice cultures were used to test whether the related structural transformations elicited by NMDA receptor stimulation are regulated by integrin-type signals. Infusing the slices with NMDA for a short period induced the expected disassembly of the cytoskeletal network, measured with antibodies that selectively recognize spectrin cleavage sites targeted by the protease calpain. Marked levels of the 150-kDa breakdown product (BDP) were produced, whereas concentrations of the parent spectrin were not changed. Interestingly, the calpain cleavage events were attenuated by 60% when integrin-type signaling was disrupted with the antagonist Gly-Arg-Gly-Asp-Ser-Pro (GRGDSP). This effect was RGDS-dependent, was largely evident in synapse-dense dendritic areas, particularly in subfield CA1, and was abolished when the NMDA exposure period was >5 min. These findings suggest that only those cytoskeletal alterations associated with brief synaptic activity are regulated by intact contact zones. AMPA-type glutamate receptors also were tested because, like spectrin, they are targets for calpain. Brief NMDA treatment caused a 15% loss of AMPA receptor GluR1 carboxytermini and this modification was augmented to 32% in the presence of GRGDSP. Thus, although blockage of matrix recognition signals decreased spectrin's susceptibility to disassembly, it increased the susceptibility of AMPA receptors to proteolysis. These data indicate that integrin-type signaling complexes are appropriately positioned to govern cytoskeletal reconfiguration while stabilizing the structural nature of AMPA receptors.
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PMID:Integrin-type signaling has a distinct influence on NMDA-induced cytoskeletal disassembly. 1070 20

Liposomes carrying both recombinant platelet membrane glycoproteins GPIa/IIa (rGPIa/IIa) and GPIb alpha (rGPIb alpha) (rGPIa/IIa-Ib alpha-liposomes), or fibrinogen (Fbg-liposomes) were prepared. Their interactions with platelets on a collagen surface under flow conditions were evaluated using a recirculating flow chamber, mounted on an epifluorescence microscope, which allows for real-time visualization of fluorescence-labeled liposomes or platelets interacting with the surface. Adhesion of platelets to the collagen surface increased with increasing the shear rate from 600 to 2400 s(-1). Also, the percentages of surface coverage of rGPIa/IIa-Ib alpha-liposomes or Fbg-liposomes increased with increasing platelet adhesion. These phenomena were attenuated by a peptide containing arginine-glycine-aspartic acid (RGD-peptide), or prostaglandin E1 (PGE), but not by a peptide containing arginine-glycine-glutamic acid (RGE-peptide). In a homogeneous solution, rGPIa/IIa-Ib alpha-liposomes and Fbg-liposomes enhanced platelet aggregation in a dose-dependent manner, as evaluated using an aggregometer. These findings suggest that rGPIa/IIa-Ib alpha-liposomes and Fbg-liposomes form aggregates at the site of injury in blood vessels, resulting in stationary adhesion together with activated platelets.
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PMID:Platelet interactions with liposomes carrying recombinant platelet membrane glycoproteins or fibrinogen: approach to platelet substitutes. 1179 31

Fluorometric cell attachment assays together with competitive inhibitors of adhesion were used to probe for the presence of integrins, a diverse family of heterodimeric cell-surface glycoproteins involved in cell-cell and cell-extracellular matrix adhesion, in the fibroblastic rainbow trout cell line, RTG-2. The adhesive properties of this cell line were evaluated. RTG-2 cells adhered poorly to TC plastic in the absence of serum but as little as 2.5% fetal bovine serum allowed over 75% of the cells to attach after 5 h. Surfaces coated with the extracellular matrix proteins collagen I, collagen IV, fibrin, fibrinogen, or fibronectin were able to support attachment of RTG-2 cells. Adhesion of RTG-2 cells to fibronectin varied linearly with fibronectin coating densities in the range 0 to 65 ng/mm(2). Oligopeptides containing the sequence Arg-Gly-Asp (RGD) caused dose-dependent inhibition of adhesion to microtiter plates coated with fibrin, fibrinogen, and fibronectin, whereas attachment to collagen I and collagen IV was less severely affected. In all cases, peptides containing Arg-Gly-Glu (RGE) or Asp-Gly-Arg (DGR) sequences caused no reduction of cell attachment. Since many integrins mediate adhesion by binding to RGD sequences in their target ligands, these results suggest the presence of integrin-like adhesion molecules on the surface of RTG-2 cells.
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PMID:Integrin-like substrate adhesion in RTG-2 cells, a fibroblastic cell line derived from rainbow trout. 1184 23

A novel disintegrin, saxatilin, was purified from Korean snake (Gloydius saxatilis) venom by means of chromatographic fractionations. We have also isolated the cDNA encoding the disintegrin using cDNA library of the snake venom gland and analyzed its complete nucleotide sequence. Saxatilin is a single-chain polypeptide composed of 73 amino acids including 12 cysteines as well as the tripeptide sequence Arg-Gly-Asp (RGD), a proposed recognition site of adhesive proteins. Molecular mass of saxatilin was determined to be 7712 Da by matrix-assisted laser desorption ionization mass spectrometry. Saxatilin inhibits glycoprotein (GP) IIb-IIIa binding to immobilized fibrinogen with IC(50) of 2.0 nM and ADP-induced platelet aggregation with IC(50) of 127 nM, respectively. The snake venom disintegrin also significantly suppresses basic fibroblast growth factor-induced human umbilical vein endothelial cell (HUVEC) proliferation, but has little effect on normal growth of the cell. Interaction of human umbilical vein cell to immobilized vitronectin is also inhibited by binding of saxatilin to alpha(v)beta(3) integrin. Adhesion of smooth muscle cells (SMCs) to vitronectin as well as vitronectin-induced migration of the cells was strongly inhibited by saxatilin. Several lines of experimental evidence suggest potential use of saxatilin for development of therapeutic agents.
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PMID:Snake venom disintegrin, saxatilin, inhibits platelet aggregation, human umbilical vein endothelial cell proliferation, and smooth muscle cell migration. 1186 11

The involvement of integrins in phagocyte spreading and phagocytosis was investigated in the compound ascidian Botryllus schlosseri. The number of spreading cells was significantly reduced when adhesion occurred in the presence of the tetrapeptide Arg--Gly--Asp--Ser (RGDS), but not of Arg--Gly--Glu--Ser (RGES) indicating the involvement of RGD-mediated adhesion mechanisms in phagocyte spreading. The significant decrease of the fraction of spreading cells in the presence of Botryllus blood plasma suggests the presence of RGD-containing molecules in the blood of our species. The increase in the same index when blood plasma-coated slides as well as fibrinogen- and fibronectin-coated coverslips were used, fits with the above hypothesis. Adhesion in the presence of RGDS leads to a consistent alteration of the actin cytoskeleton, in agreement with the known role of integrin adhesion in microfilament organization. Phagocytosis was greatly reduced by RGDS in the incubation medium, but not by RGES, and was significantly increased by coating yeast cells with fibronectin or blood plasma. Both spreading and phagocytic capability were severely inhibited by wortmannin, suggesting the importance of phosphatidylinositol-3-kinase in integrin-mediated signal transduction in ascidians.
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PMID:Phagocyte spreading and phagocytosis in the compound ascidian Botryllus schlosseri: evidence for an integrin-like, RGD-dependent recognition mechanism. 1188 49

Del1 is a matrix protein transiently expressed by embryonic endothelial cells. It was recently demonstrated that vascular endothelial cells adhere and interact with Del1 through alpha(v)beta(3)- integrins, providing an autocrine angiogenic signaling pathway in this cell type. To determine whether Del1 might signal to other cell types in the vessel wall in a paracrine fashion, studies were conducted with vascular smooth muscle cells (VSMC). Del1 promoted adhesion and migration of VSMC in a dose-dependent fashion. These functions were mediated through alpha(v)beta(3)-integrins, as the vitronectin receptor inhibitory peptide containing penacillamine (PCN) arginine-glycine-aspartic acid (PCN-RGD) and an antibody specific for the alpha(v)beta(3)-integrin specifically blocked both adhesion and migration. Adhesion of VSMC to Del1 was associated with organization of actin filaments and formation of focal contacts enriched in vinculin and alpha(v)beta(3). Furthermore, Del1 supported VSMC proliferation at least in part by inhibiting these cells from undergoing apoptosis. These data, in conjunction with evidence that Del1 expression is reactivated in vascular injury, suggest that Del1 may have a paracrine role in vessel wall development and remodeling.
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PMID:Del1 mediates VSMC adhesion, migration, and proliferation through interaction with integrin alpha(v)beta(3). 1195 60


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