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

p130Cas (Cas) has been recently identified as a 130-kDa protein that is highly phosphorylated on tyrosine residues and is stably associated with p47v-crk (v-Crk) and p60v-src (v-Src) oncogene products in cells transformed by the respective genes. Cas is a novel signaling molecule having a single Src homology (SH) 3 domain and a cluster of multiple SH2-binding motifs. While the tight association of Cas with v-Crk and v-Src is strongly suggestive of a significant role in regulating cellular transformation, the function of Cas in normal untransformed cells is totally unknown. We report here that cell adhesion to fibronectin rapidly promotes tyrosine phosphorylation of Cas in human and rat fibroblast cell lines. The response was equally induced by cell adhesion to plates coated with vitronectin, laminin, and collagen but not by cell attachment to nonspecific substrate poly-L-lysine. The kinetic profile of Cas phosphorylation was almost identical with that of tyrosine phosphorylation of focal adhesion kinase pp125FAK (Fak), which is well known to be activated subsequent to integrin-mediated cell adhesion. Adhesion-dependent Cas phosphorylation was completely inhibited by treating cells with cytochalasin D, an agent that disrupts polymerization of actin stress fibers. These results suggest that tyrosine phosphorylation of Cas is stimulated by normal cell adhesion in close association with Fak phosphorylation and the formation of actin stress fibers. In v-Src- or v-Crk-transformed cells, however, the tyrosine phosphorylation of Cas is markedly increased in an adhesion-independent manner that is insensitive to treatment with cytochalasin D. Thus, Cas plays a role in signaling pathways mediated by cell adhesion as well as by transformation. We propose that Cas may amplify and propagate integrin-mediated signals by interacting with SH2-containing molecule(s).
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PMID:Integrin-mediated cell adhesion promotes tyrosine phosphorylation of p130Cas, a Src homology 3-containing molecule having multiple Src homology 2-binding motifs. 754 Oct 40

Adhesion of cells to the extracellular matrix leads to an increase in the tyrosine phosphorylation of a specific set of proteins, three of which have now been identified as the focal adhesion proteins pp125FAK, paxillin and tensin. In addition, we have previously noted the adhesion-induced tyrosine phosphorylation of a fourth protein, with an apparent molecular mass of 130. As in the case of FAK, paxillin and tensin, a 130 kDa protein is also found to be highly tyrosine phosphorylated in Rous sarcoma virus (RSV)-transformed cells. This protein forms a stable complex with pp60src and is directly phosphorylated by activated forms of c-src. Using a monoclonal antibody (mAb 4F4) specific for the src-associated p130 we show that p130 is also phosphorylated in response to cell adhesion. Immunoprecipitation of p130 followed by an anti-phosphotyrosine immunoblot revealed that adhesion of rat embryo fibroblasts (REF52) to fibronectin (FN) led to a significant increase in the phosphotyrosine content of p130. Furthermore, a comparison of cell lysates before and after immunoprecipitation confirmed the absence of tyrosine phosphorylated p130 from lysates immunoprecipitated with mAb 4F4. Immunofluorescence staining of REF52s revealed that p130 is found in focal adhesions as well as along stress fibers in a pattern reminiscent of that exhibited by alpha-actinin. In addition, in many cells, we found significant staining in the nucleus, but evidence is presented that the nuclear staining is not due to tyrosine phosphorylated p130. Finally, unlike pp125FAK, p130 does not appear to be itself a kinase as evidence by immune-complex kinase assays carried out in the presence or absence of exogenous substrates.
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PMID:Adhesion-induced tyrosine phosphorylation of the p130 src substrate. 754 55

Adhesion to the adhesion protein, VCAM-1, on vascular endothelium is proposed to be an important factor in the selective accumulation of eosinophils at sites of allergic inflammation. To determine whether eosinophil adhesion to VCAM-1 is also associated with an alteration of eosinophil function, human peripheral blood eosinophils were isolated from allergic donors and incubated in VCAM-1-coated wells. Spontaneous adherence of isolated eosinophils to VCAM-1-coated wells was greater than cells incubated in FCS-treated control wells (38.0 +/- 1.6% vs 17.1 +/- 1.9%, n = 16, p < 0.0001). In addition, eosinophils incubated in VCAM-1-coated wells spontaneously generated modest but significant amounts of superoxide anion (O2-; 2.0 +/- 1.3 vs 00.5 +/- 0.5 nmol/5 x 10(5) cells, n = 9, p = 0.029). Moreover, when 100 nM FMLP was added to eosinophils in the presence of VCAM-1, significantly greater O2- generation occurred (7.2 +/- 0.9 vs 5.4 +/- 1.0 (FCS control) nmol/5 x 10(5) cells, n = 9, p = 0.009). Adhesion, as well as the spontaneous and enhanced O2- generation to FMLP activation, was blocked by the monoclonal anti-alpha 4 integrin Ab, HP 1/2, implying involvement of an alpha 4 integrin-VCAM-1 interaction. In contrast, the anti-CD18 mAb, L130, inhibited the spontaneous and enhanced O2- generation to FMLP without affecting adhesion, suggesting an involvement of CD18 molecule(s) only in VCAM-1-enhanced respiratory burst. Finally, 1 microM genistein, a tyrosine kinase inhibitor suppressed the VCAM-1-enhancing effect on eosinophil O2- generation and VCAM-1-induced tyrosine phosphorylation, suggesting a role for tyrosine phosphorylation in this eosinophil functional up-regulation. Our observations suggest that eosinophil adhesion to VCAM-1 may be an important step in determining the eventual functional activity of these cells as they migrate from the circulation to the airways and contribute to the allergic inflammatory process.
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PMID:Eosinophil adhesion to vascular cell adhesion molecule-1 activates superoxide anion generation. 754 40

Non-malignant rat liver epithelial cell line BRL was reported to adhere to a substrate by fibronectin. DNA synthesis of these cells was induced by adhesion to a substrate by fibronectin, while DNA synthesis in non-adhered cells was not observed. These results indicated that DNA synthesis in BRL cells is inducible by the cell adhesion signaling. Adhesion-inducible DNA synthesis was strongly inhibited by Herbimycin A. In contrast, vanadate showed the tendency to promote adhesion-inducible DNA synthesis. These results suggest that DNA synthesis caused by the cell adhesion in these cells was regulated by both phosphorylation and dephosphorylation at tyrosine residue.
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PMID:Adhesion-inducible DNA synthesis regulated by tyrosine phosphorylation/dephosphorylation. 757 55

Adhesion of B lymphocytes within the different compartments of secondary lymphoid organs is essential for the function of the humoral immune response. It is not currently known how the temporary immobilization of B cells in distinct areas of this complex microenvironment is regulated. The present study aimed at defining B cell antigens that initiate binding of B cells to human tonsil sections in situ. Engaging the B cell antigens CD19 and target of an antiproliferative antibody 1 (TAPA-1) with monoclonal antibodies induced adhesion of these B cells to the interfollicular stroma. This binding occurred through the integrin alpha 4 beta 1 on the B cell surface and via the extracellular matrix protein fibronectin expressed in the interfollicular compartment of the tonsil. Signaling through either antigen, CD19 or TAPA-1, depended on tyrosine kinases. Binding induced by engaging CD19 required an intact cytoskeleton, whereas TAPA-1-transmitted adhesion did not. We suggest that CD19 and TAPA-1 have a novel and unique function by regulating an alpha 4 beta 1/fibronectin-mediated binding of B cells to the interfollicular stroma of lymphoid tissues.
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PMID:Engaging CD19 or target of an antiproliferative antibody 1 on human B lymphocytes induces binding of B cells to the interfollicular stroma of human tonsils via integrin alpha 4/beta 1 and fibronectin. 759 90

Modification of non-immunological cell adhesion properties plays a major role in the decrease in metastatic ability observed after transfection of the H-2Kb gene in H-2-negative B16-derived melanoma clone cells. To investigate the role played by different class-I major histocompatibility complex (MHC) genes on non-immunological properties relevant for metastasis, transfection with the H-2Db gene alone or in conjunction with the H-2Kb gene was performed. H-2Db gene transfection did not modify either metastatic potential or non-immunological cell adhesion properties. Double KbDb transfectants showed a decreased metastatic ability when compared to control clones and to Db transfectants; a decrease in homotypic adhesive ability was also observed, even though not in all clones studied: therefore expression of the Db gene is also relevant. The mechanisms of homotypic cell adhesion were studied and found to be dependent upon temperature and divalent cations. Adhesion was partially inhibited by an antiserum directed against the beta 1 integrin subunit, whereas anti-alpha IIb beta 3 was ineffective. Cell pre-treatment with anti-beta 1 serum reduced metastatic ability. A decreased expression of alpha 4 and alpha 6 integrin subunits was observed in Kb clones, whereas no difference in the levels of some homophilic cell adhesion molecules, such as N-CAM and alpha IIb beta 3, was found. Adhesion required the activity of tyrosine kinases, as suggested by the decreased adhesive properties and impaired metastatic ability of cells pre-treated with the tyrosine-kinase-inhibitor genistein. These results are compatible with involvement of integrin molecules of the beta 1 family in the adhesive ability of these cells. Our data show that: (a) immunological and non-immunological effects of MHC transfection are correlated and depend on the class-I gene used, suggesting that MHC gene therapy can be highly successful only if appropriate MHC genes are transfected; (b) non-immunological cell-adhesion properties modified after MHC transfection could be related to an impairment of integrin-mediated adhesive interactions.
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PMID:H-2Kb and H-2Db gene transfections in B16 melanoma differently affect non-immunological properties relevant to the metastatic process. Involvement of integrin molecules. 792 28

Adhesion of human neuroblastoma cells (SK-N-SH clone SY5Y) to laminin or collagen type IV promotes tyrosine phosphorylation of a group of proteins with molecular mass ranging from 100 to 130 kDa and of a protein of 180 kDa. The same pattern of tyrosine phosphorylation was observed when SY5Y cells were allowed to adhere to culture dishes coated with monoclonal antibodies directed to the integrin subunits expressed in the cells, alpha 1, alpha 3, and beta 1, indicating that these receptors are responsible for this signaling mechanism. Using specific antibodies we identified the focal adhesion kinase p125FAK as a component of the 100- to 130-kDa phosphoproteins. Treatment with genistein or herbimycin A, two specific tyrosine kinase inhibitors, greatly reduced the tyrosine phosphorylation of the 100- to 130- and the 180-kDa proteins in response to laminin or collagen IV. Concomitantly, neurite outgrowth on the matrix proteins was strongly inhibited. This effect was observed in two distinct neuroblastoma cell lines, SY5Y and SK-N-BE. Genistein and herbimycin A treatment did not affect cell viability nor cause retraction of preformed neurites. These data suggest that matrix-induced tyrosine phosphorylation events are involved in neurite extension.
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PMID:Role of tyrosine phosphorylation in matrix-induced neurite outgrowth in human neuroblastoma cells. 808 34

Adhesion of CD8+ CTL to purified class I proteins has been shown to be regulated by the TCR: nonactivated CTL do not adhere to immobilized class I proteins (non-Ag), but adhesion becomes readily detectable upon treatment of the CTL with fluid-phase anti-TCR mAb. Signals for up-regulating CD8 adhesion do not appear to involve products of the PI pathway, as neither increased production of inositol phosphates or mobilization of [Ca2+]i can be detected in response to the fluid-phase anti-TCR mAb, but both occur when the CTL then bind to class I protein. The lack of a role for phosphoinositide pathway products in up-regulating CD8 was confirmed by the inability of phorbol ester or calcium ionophore to substitute for TCR mAb in triggering adhesion to class I proteins. Instead, both phorbol ester and calcium ionophore inhibited the anti-TCR mAb-stimulated adhesion to class I. Inhibitors of protein tyrosine kinases also block TCR-activated, CD8-dependent adhesion to class I, and concomitantly block inositol phosphate release, Ca2+ mobilization and degranulation. Inhibition of signaling and response does not appear to be caused solely by the inhibition of adhesion to class I, however, because these inhibitors also block signaling in response to immobilized anti-TCR mAb under conditions in which binding of other receptors to their ligands is not necessary to initiate phosphoinositide hydrolysis and degranulation. These results lend further support for a model in which CTL activation involves a cascade of adhesion and signaling events initiated by the TCR and propagated by CD8 and additional cell-surface receptors.
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PMID:Signals for activation of CD8-dependent adhesion and costimulation in CTLs. 815 59

The integrin family of heterodimeric cell surface receptors play critical roles in multiple biological processes by mediating cellular adhesion to the extracellular matrix (ECM). Adhesion triggers intracellular signaling cascades, including tyrosine phosphorylation and elevation of [Ca2+]i. The Focal Adhesion Kinase (FAK or pp125FAK), a protein tyrosine kinase that colocalizes with integrins in cellular focal adhesions, is a prime candidate for a mediator of integrin signaling events. Here we report an analysis of the domain structure of FAK in which we have identified a contiguous stretch of 159 amino acids within the COOH terminus essential for correct subcellular localization. When placed in the context of an unrelated cytosolic protein, this Focal Adhesion Targeting (FAT) sequence functions to efficiently mediate the focal adhesion localization of this fusion protein. Furthermore, this analysis suggests that pp125FAK cannot be activated oncogenically by mutation. This result could be explained if pp125FK either exhibits a narrow substrate specificity or is diametrically opposed by cellular phosphatases or other cellular processes.
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PMID:Identification of sequences required for the efficient localization of the focal adhesion kinase, pp125FAK, to cellular focal adhesions. 822 54

Adhesion of human platelets to collagen under arterial flow conditions mediated by the alpha 2 beta 1 integrin increased tyrosine phosphorylation of several proteins, one of which was the focal adhesion tyrosine kinase, pp125FAK. Tyrosine phosphorylation of pp125FAK did not occur in non-adherent flowing platelets or in platelets attached to poly(L-lysine). Neither adhesion nor tyrosine phosphorylation was affected by pretreatment of platelets with GRGDSP peptide or by anti-alpha IIb beta 3 monoclonal antibody P2. Adherent platelets retained their discoid shape, suggesting that induction of pp125FAK precedes platelet spreading. The tyrosine kinase inhibitor erbstatin decreased tyrosine phosphorylation in non-stimulated platelets and blocked platelet adhesion. These results suggest that pp125FAK plays an important role in platelet adhesion to collagen via the alpha 2 beta 1 integrin.
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PMID:Platelet adhesion to collagen via the alpha 2 beta 1 integrin under arterial flow conditions causes rapid tyrosine phosphorylation of pp125FAK. 828 49


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