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PubMed2002

[Calcium and cellular adhesion mechanism--involvement of intracellular calcium to cell adhesion].

Cell to cell and cell to extracellular matrix adhesion play an essential role in embryogenesis, differentiation, morphological development and disease processes. Adhesion processes are affected by two reverse directional signaling: expression of adhesion molecules is regulated by inside-out signaling and the molecules transduce extracellular information into cytoplasm by "outside-in" signaling. Cadherins are a family of Ca(2+)-dependent cell-cell adhesion molecules that are important for the mutual association of vertebrate cells. During cell differentiation, for example, the amount or the nature of the cell-surface cadherins and other adhesion molecules change, affecting many aspects of cell-cell adhesion and cell migration.

English Abstract↗
PubMed1999

Extracellular adenosine triphosphate affects neural cell adhesion molecule (NCAM)-mediated cell adhesion and neurite outgrowth.

The neural cell adhesion molecule (NCAM) plays an important role in synaptic plasticity in embryonic and adult brain. Recently, it has been demonstrated that NCAM is capable of binding and hydrolyzing extracellular ATP. The purpose of the present study was to evaluate the role of extracellular ATP in NCAM-mediated cellular adhesion and neurite outgrowth. We here show that extracellularly added adenosine triphosphate (ATP) and its structural analogues, adenosine-5'-O-(3-thiothiophosphate), beta, gamma-methylenadenosine-5'-triphosphate, beta, gamma-imidoadenosine-5-triphosphate, and UTP, in varying degrees inhibited aggregation of hippocampal neurons. Rat glial BT4Cn cells are unable to aggregate when grown on agar but acquire this capacity when transfected with NCAM. However, addition of extracellular ATP to NCAM-transfected BT4Cn cells inhibited aggregation. Furthermore, neurite outgrowth from hippocampal neurons in cultures allowing NCAM-homophilic interactions was inhibited by addition of extracellular nucleotides. These findings indicate that NCAM-mediated adhesion may be modulated by extracellular ATP. Moreover, extracellularly added ATP stimulated neurite outgrowth from hippocampal neurons under conditions non-permissive for NCAM-homophilic interactions, and neurite outgrowth stimulated by extracellular ATP could be inhibited by a synthetic peptide corresponding to the so-called cell adhesion molecule homology domain (CHD) of the fibroblast growth factor receptor (FGFR) and by FGFR antibodies binding to this domain. Antibodies against the fibronectin type-III homology modules of NCAM, in which a putative site for ATP binding and hydrolysis is located, also abolished the neurite outgrowth-promoting effect of ATP. The non-hydrolyzable analogues of ATP all strongly inhibited neurite outgrowth. Our results indicate that extracellular ATP may be involved in synaptic plasticity through a modulation of NCAM-mediated adhesion and neurite outgrowth.

Adenosine Diphosphate↗
PubMed2005

Carbohydrates located on the top of the "cap" contribute to the adhesive and enzymatic functions of vascular adhesion protein-1.

Vascular adhesion protein 1 (VAP-1) is an endothelial adhesion molecule with an enzymatic activity. It deaminates biogenic amines, resulting in the formation of aldehydes and hydrogen peroxide. During the enzymatic reaction a transient Schiff base is formed between endothelial VAP-1 and its leukocytic ligand, and this interaction is important for lymphocyte adhesion. VAP-1 monomer has six potential N-linked, and three putative O-linked glycosylation sites and an SSSS sequence potentially forming an attachment site for an adjacent O-linked site. In this work we modeled the carbohydrate decorations on a structural model of VAP-1, and studied which of those potential glycosylation sites are utilized, and whether those decorations accessible to a lymphocyte ligand are important in lymphocyte adhesion and enzymatic activity of VAP-1. We show that, unlike the O-linked attachment sites, all six N-linked glycosylation sites are in use. Furthermore, mutation of the N-linked attachment sites strategically located on the top of the molecule reduces lymphocyte adhesion in non-static conditions, and enhances the catalytic activity of membrane-bound human VAP-1 in static conditions, suggesting that glycosylation regulates the functional properties of VAP-1.

Amine Oxidase (Copper-Containing)↗
PubMed2007

Upregulation of intracellular adhesion molecule (ICAM)-1 and vascular cell adhesion molecule (VCAM)-1 after unilateral nerve injury in the peripheral taste system.

In the peripheral taste system, activated macrophages are recruited to both sides of the tongue after unilateral sectioning of the chorda tympani nerve (CT). Neural degeneration elicits macrophage entry in other systems by upregulating vascular adhesion molecules. We hypothesized that CT sectioning leads to a bilateral increase in intracellular adhesion molecule (ICAM)-1 and vascular cell adhesion molecule (VCAM)-1 expression on lingual vessels. To test this hypothesis, rats were euthanized at time points from 6 hr to 7 days post-sectioning. Frozen sections of tongue were processed for immunohistochemical staining for ICAM-1 and VCAM-1. Tongue homogenates from additional rats were analyzed with ELISA. ICAM-1 expression increases first on the denervated side of the tongue at 24 hr post-section and then on the uninjured side at 48 hr post-section. ICAM-1 remains elevated through Day 7 post-sectioning on both sides of the tongue. Dietary sodium restriction, which prevents the macrophage response to nerve sectioning, had no effect on ICAM-1 levels. VCAM-1+ vessels are increased on the denervated side of the tongue at 24-48 hr post-section in control-fed rats. However, dietary sodium restriction prevents the increase. These results indicate that vascular adhesion molecules are differentially regulated by CT sectioning. We suggest that macrophage entry, migration, and modulation of taste function are downstream of dynamic expression of adhesion molecules.

Animals↗
PubMed1996

Osteoblast adhesion to orthopaedic implant alloys: effects of cell adhesion molecules and diamond-like carbon coating.

In total joint arthroplasty, long-term outcomes depend in part on the biocompatibility of implant alloys. This study analyzed effects of surface finish and diamond-like carbon coating on osteoblast cell adhesion to polished titanium-aluminum-vanadium and polished or grit-blasted cobalt-chromium-molybdenum alloys. Osteoblast binding was tested in the presence and absence of the cell adhesion proteins fibronectin, laminin, fibrinogen, and vitronectin and was quantified by measurement of DNA content. Although adherence occurred in serum-free medium, maximal osteoblast binding required serum and was similar for titanium and cobalt alloys at 2 and 12 hours. With the grit-blasted cobalt alloy, cell binding was reduced 48% (p < 0.05) by 24 hours. Coating the alloys with diamond-like carbon did not alter osteoblast adhesion, whereas fibronectin pretreatment increased cell binding 2.6-fold (p < 0.05). In contrast, fibrinogen, vitronectin, and laminin did not enhance cell adhesion. These results support the hypothesis that cell adhesion proteins can modify cell binding to orthopaedic alloys. Although osteoblast binding was not affected by the presence of diamond-like carbon, this coating substance may influence other longer term processes, such as bone formation, and deserves further study.

Alloys↗
PubMed2001

Increased expression of intercellular adhesion molecule-1 and mucosal adhesion molecule alpha4beta7 integrin in small intestinal mucosa of adult patients with food allergy.

The mechanisms of adverse reactions to foods in the gastrointestinal tract are poorly understood. Previous studies of other atopic diseases and animal models suggest that adhesion molecules and mucosal lymphocytes may be implicated in the pathogenesis of food allergy (FA). The aim of our study was to investigate the expression of adhesion molecules and mucosal lymphocytes in duodena of patients with food allergies and of controls. Ten patients with FA to cereals (wheat, oats, and rye) or cow's milk and 9 control patients were included in the study. Quantitative analysis and immunohistochemical stainings for two pairs of adhesion molecules (intercellular adhesion molecule-1 (ICAM-1), lymphocyte function-associated antigen-1 (LFA-1), alpha4beta7 integrin, and mucosal addressin cell adhesion molecule (MAdCAM-1) and lymphocyte markers on endoscopic duodenal biopsy specimens were performed. The villous structure and density of LFA-1-positive cells were normal in every biopsy specimen, but the patients had significantly more alpha4beta7+ cells in the intraepithelial space (P = 0.01). The expression of ICAM-1 in the lamina propria of patients with FA was also substantially increased (P = 0.003); however, staining with MAdCAM showed no intergroup difference. Moreover, we found significantly increased CD4+ and HLA-DR+ cells in the lamina propria of patients, in comparison to the controls, P = 0.05 and P = 0.04, respectively. The densities of CD3, CD8, HLA-DP, T cell receptor alphabeta+ and gammadelta+ cells and IgA-, IgA1-, and IgA2-containing cells did not differ in the two groups studied. Our results suggest that the increased expression of ICAM-1 and alpha4beta7 integrin may play an important role in the pathogenesis of food hypersensitivity and with the elevation of CD4- and HLA-DR-positive cells reflect a stage of inflammation in the structurally normal intestines.

Adolescent↗
PubMed2002

A novel Dictyostelium gene encoding multiple repeats of adhesion inhibitor-like domains has effects on cell-cell and cell-substrate adhesion.

The Dictyostelium protein AmpA (adhesion modulation protein A) is encoded by the gene originally identified by the D11 cDNA clone. AmpA contains repeated domains homologous to a variety of proteins that influence cell adhesion. The protein accumulates during development, reaching a maximal level at the finger stage. Much of the AmpA protein is found extracellularly during development, and in culminants, AmpA is found in association with anterior-like cells. Characterization of an ampA- strain generated by gene replacement reveals a significant increase in cell-cell clumping when cells are starved in nonnutrient buffer suspensions. Developing ampA- cells are also more adhesive to the underlying substrate and are delayed in developmental progression, with the severity of the delay increasing as cells are grown in the presence of bacteria or on tissue culture dishes rather than in suspension culture. Reintroduction of the ampA gene rescues the developmental defects of ampA- cells; however, expression of additional copies of the gene in wild-type cells results in more severe developmental delays and decreased clumping in suspension culture. We propose that the AmpA protein functions as an anti-adhesive to limit cell-cell and cell-substrate adhesion during development and thus facilitates cell migration during morphogenesis.

Agar↗
PubMed1994

Stimulation of intercellular adhesion molecule-1 (ICAM-1) antigen expression and shedding by interferon-gamma and phorbol ester in human renal carcinoma cell cultures: relation to peripheral blood mononuclear cell adhesion.

In the present study we investigated the effect of interferon-gamma (IFN-gamma) and phorbol-12-myristate 13 acetate (PMA) on intercellular adhesion molecule-1 (ICAM-1) antigen expression and shedding in human renal carcinoma cell cultures. We also examined the functional consequences of ICAM-1 antigen expression and soluble ICAM-1 molecules on the adhesion of peripheral blood mononuclear cells (PBMC). Incubation of the human renal carcinoma cell line CaKi-1 with IFN-gamma or PMA enhanced ICAM-1 antigen expression. The calcium ionophore, 4-bromo-calcium ionophore A23187 (Bromo-A23187) significantly enhanced the IFN-gamma and PMA effect. Soluble ICAM-1 (sICAM-1) was detected in the supernatants of stimulated but not unstimulated cultures, and correlated significantly with cellular expression. Using 51Cr-labelled peripheral blood mononuclear cells in a cell adhesion assay, we demonstrated increased adhesion in IFN-gamma-treated CaKi-1 cultures, which was augmented by Bromo-A23187. This adhesion was blocked by preincubation of CaKi-1 cells with monoclonal antibody against ICAM-1 or by preincubation of PBMC with either monoclonal antibody against leucocyte function associated antigen-1 alpha (LFA-1 alpha), a major receptor for ICAM-1, supernatants from treated cultures or purified sICAM-1 molecules. Thus, shedding of ICAM-1 may play a role during the escape from immunosurveillance by renal carcinoma cells.

Antigens, Neoplasm↗
PubMed1994

A truncated recombinant intercellular adhesion molecule-1 inhibits adhesion of leukemic cell lines to upregulated endothelial cells.

Intercellular adhesion molecule-1, a member of the immunoglobulin supergene family, is the ligand for the integrin lymphocyte function associated antigen-1. Intercellular adhesion molecule-1 and lymphocyte function associated antigen-1 binding interactions mediate leukocyte adherence and migration. Previous work has shown that the adherence of lymphocyte function associated antigen-1 is directed to the first immunoglobulinlike domain of the endothelial cell surface protein intracellular adhesion molecule-1. We have constructed a truncated intercellular adhesion molecule-1 gene encoding the first 185 amino acids from the amino terminus and overexpressed it in Escherichia coli. The recombinant protein was purified from insoluble inclusion bodies and refolded into an active conformation by a denaturation/renaturation cycle. The identity of the protein was confirmed by microsequencing and by Western blot analysis using a polyclonal antibody to ICAM-1. We have demonstrated that this soluble region of the otherwise membrane-bound ligand is an inhibitor of Molt or HL-60 cell adhesion to cytokine-stimulated endothelial cells.

Amino Acid Sequence↗
PubMed1995

The cytoplasmic domain of the cell adhesion molecule L1 is not required for homophilic adhesion.

L1 is a highly conserved cell adhesion molecule with complete homology of the cytoplasmic domain between the known mammalian protein sequences. Since the cytoplasmic domains of other adhesion molecules have been shown to influence adhesion, we have investigated the effects of deletion of the cytoplasmic domain on the ability of L1 to mediate homophilic adhesion. Full length L1 and a truncated L1, lacking 95% of the cytoplasmic domain, were expressed in myeloma cells. Independent stable transfectants were assayed for the ability to form aggregates. Myelomas expressing L1 lacking the cytoplasmic domain were able to form cell aggregates as well as the myelomas expressing full length L1. Cell aggregate formation was correlated with the level of L1 expression, and the aggregation could be blocked by anti-L1 Fabs. Similar results were obtained in adhesion assays of the myeloma cells to substrate-bound L1. These results indicate that the cytoplasmic domain of L1 is not required for homophilic interactions.

Amino Acid Sequence↗
PubMed1999

Determination of the adhesive capability of canine polymorphonuclear neutrophil granulocytes using a fluorometric microtiter plate cellular adhesion assay.

A rapid fluorometric cellular adhesion assay in microtiter plates was evaluated for canine polymorphonuclear neutrophil granulocytes (PMN) using the fluorescent indicator calcein acetoxymethyl ester (Calcein AM). Optimum adhesive responsiveness occurred in bovine serum albumin (BSA)-coated plates after 30 min incubation at 37 degrees C with 5 x 10(5) PMN in 100 microl per well using phorbol myristate acetate (PMA, 100 ng/ml) as stimulant. The adhesive responsiveness for 15 laboratory beagle dogs was determined and the mean percentage of adherence for unstimulated (2.9%) and stimulated (74.3%) PMN and corresponding 95% confidence intervals was determined. The mean intra-assay coefficient of variation (CVintra) for unstimulated and stimulated adhesion in the assay was: CVintra = 12.9% and CVintra = 4.1%, respectively. The mean inter-assay coefficient of variation (CVinter) for unstimulated and stimulated adhesion, respectively, in the assay was: CVinter = 22.9% and CVinter = 5.6%. The assay was highly reproducible and labelling with Calcein AM neither reduced PMN viability nor activated the PMN.

Adhesiveness↗
PubMed1996

Alterations in soluble intercellular adhesion molecule-1 and vascular cell adhesion molecule-1 in hemodialysis patients.

Hemodialysis (HD) patients can develop acute reactions during treatment as well as increased long-term susceptibility to infections and malignancies. Abnormalities in leukocyte adhesion may contribute to these processes. Recently, serum levels of soluble adhesion molecules have been detected in circulating blood of normal subjects and in patients with chronic renal failure. We studied the effects of a single dialysis session with new cuprophane membrane on the soluble (s) form of intracellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1), two adhesion molecules with a variety of immunologic roles. Significant elevations in both sICAM-1 (523 +/- 61 v 304 +/- 45 [SEM] ng/mL, P < 0.05) and sVCAM-1 (2,055 +/- 270 v 1,189 +/- 149 ng/mL, P < 0.05) were observed in HD patients at baseline compared with controls. Both sICAM-1 and sVCAM-1 levels decreased after a 3-hour HD session (P < 0.001). Early in HD, sICAM-1 levels, though lower than predialysis, were elevated in the exit line of the dialyzer compared with entrance (339 +/- 64 v 259 +/- 53 ng/mL, P < 0.001), whereas sVCAM-1 was decreased on the exit line compared with entrance (639 +/- 90 v 932 +/- 92 ng/mL, P < 0.001). Because ICAM-1 and VCAM-1 are important for many leukocyte functions, alterations in serum levels of sICAM-1 and sVCAM-1 may play a role in the immunologic consequences of uremia and HD treatment.

Case-Control Studies↗
PubMed1997

Antioxidants inhibit the expression of intercellular cell adhesion molecule-1 and vascular cell adhesion molecule-1 induced by oxidized LDL on human umbilical vein endothelial cells.

The oxidative modification of low density lipoprotein (LDL) and the endothelial expression of adhesion molecules are key events in the pathogenesis of atherosclerosis. In this study we evaluated the effect of oxidized LDL on the expression of intercellular cell adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1), and E-selectin on human umbilical vein endothelial cells (HUVECs). The hypothesis that oxidized LDL functions as a prooxidant signal was also evaluated, by studying the effect of different radical-scavenging antioxidants on expression of adhesion molecules. LDL was oxidized by using Cu2+, HUVECs or phospholipase A2 (PLA2)/ soybean lipoxygenase (SLO), the degree of oxidation being measured as thiobarbituric acid-reactive substances (TBARS) and conjugated dienes (CD). Exposure of 200 micrograms/ml of native LDL to 1 microns Cu2+, HUVECs and to PLA2/ SLO resulted in four- to fivefold higher levels of TBARS and CD than in native LDL. Cu(2+)-(1 microM), HUVEC-, and PLA2/SLO-oxidized LDL caused a dose-dependent, significant increase of ICAM-1 and VCAM-1 (p < .01). The expression of E-selectin did not change. LDL oxidized with a 2.5 and 5 microM Cu2+ did not increase ICAM-1 and VCAM-1 significantly. Both the Cu(2+)- and HUVEC-oxidized LDL, subjected to dialysis and ultrafiltration, induced ICAM-1 and VCAM-1 expression. After incubation with the ultrafiltrate, the expression of ICAM-1 and VCAM-1 was not significantly different from that obtained with native LDL. LDL pretreated with different antioxidants (vitamin E and probucol) and subjected to oxidation by Cu2+ and HUVECs induced a significantly lower expression of ICAM-1 and VCAM-1 than nonloaded LDL (p < .01). The pretreatment of HUVECs with vitamin E and probucol significantly reduced the expression of VCAM-1 on HUVECs induced by oxidized LDL (p < .01); the effect on ICAM-1 was much less evident. In conclusion, oxidized LDL can induce the expression of different adhesion molecules on HUVECs; this induction can be prevented by pretreating either the LDL or the cells with radical-scavenging antioxidant.

Antioxidants↗
PubMed1994

Lymphocyte activation status, expression of adhesion molecules and adhesion to human endothelium in rheumatoid arthritis--relationship to disease activity.

The synovial tissue of patients with rheumatoid arthritis (RA) is characterized by infiltration with inflammatory cells, mainly memory helper cells (CD4+CD29+). An important initiating step in tissue infiltration is the adhesion of peripheral blood lymphocytes to the vascular endothelium. Therefore, we studied lymphocyte-endothelium adhesion in 40 RA patients and in 19 controls by a sensitive fluorimetric assay, using human umbilical vascular endothelial cells. Furthermore, expression of adhesion molecules VLA (CD29) and LFA-1 (CD11a) on CD4+ and CD8+ T cells was determined. In order to evaluate the activation state of lymphocytes, the soluble interleukin-2 receptor (sIL2R) was measured. The relationship to disease activity was evaluated using the Ritchie articular index. RA patients had a higher percentage of CD4+ cells (p < 0.005) and a lower percentage of CD8+ cells (p < 0.001) than controls did. The CD4+CD29+/CD4+CD29- ratio and the CD8+CD29+/CD8+CD29- ratio were increased in patients with active RA (p < 0.01 and p < 0.05, respectively) and in patients with inactive disease (p = 0.09 and p < 0.005, respectively) compared with controls. LFA-1 (CD11a) was present on almost all T lymphocytes and its density did not differ between patients and controls. Serum levels of sIL2R were significantly higher in both patient groups compared with controls (p < 0.0005); patients with active disease showed significantly higher levels than patients with inactive disease (p < 0.05). Lymphocyte-endothelium adhesion was not increased in patients, although the expression of the adhesion molecule CD29 on T lymphocytes of RA patients was higher.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1997

Leukocyte adhesion: CD11/CD18 integrins and intercellular adhesion molecules.

Leukocyte integrins and intercellular adhesion molecules play pivotal roles in leukocyte adhesion to target cells and extracellular matrices. Recently, novel intercellular adhesion molecules have been identified, and much information has been obtained on the structures and binding sites of leukocyte integrins and of intercellular adhesion molecules. Furthermore, much progress has been made in the study of integrin activation and the role of leukocyte adhesion molecules in disease.

Animals↗
PubMed1998

Hypoxia facilitates tumour cell detachment by reducing expression of surface adhesion molecules and adhesion to extracellular matrices without loss of cell viability.

The effects of acute hypoxia on integrin expression and adhesion to extracellular matrix proteins were investigated in two human melanoma cell lines, HMB-2 and DX3, and a human adenocarcinoma cell line, HT29. Exposure to hypoxia caused a significant down-regulation of cell surface integrins and an associated decrease in cell adhesion. Loss of cell adhesion and integrin expression were transient and levels returned to normal within 24 h of reoxygenation. Other cell adhesion molecules, such as CD44 and N-CAM, were also down-regulated after exposure of cells to hypoxia. Acute exposure to hypoxia of cells at confluence caused rapid cell detachment. Cell detachment preceded loss of viability. Detached HMB-2 and DX3 cells completely recovered upon reoxygenation, and floating cells re-attached and continued to grow irrespective of whether they were left in the original glass dishes or transferred to new culture vessels, while detached HT29 cells partly recovered upon reoxygenation. Cell detachment after decreased adhesion appears to be a stress response, which may be a factor enabling malignant cells to escape hypoxia in vivo, with the potential to form new foci of tumour growth.

Cell Adhesion↗
PubMed2006

Soluble intercellular adhesion molecules, soluble vascular cell adhesion molecules, and risk of coronary heart disease.

OBJECTIVE: We examined the association of circulating levels of soluble intercellular adhesion molecules (sICAM-1) and soluble vascular cell adhesion molecules (sVCAM-1) with coronary heart disease (CHD) risk factors and whether the adhesion molecules alone, and in combination, can serve as predictors of coronary CHD. RESEARCH METHODS AND PROCEDURES: Among 18,225 men from the Health Professional Follow-up Study who provided blood in 1994, we documented 266 incidents of non-fatal myocardial infarction or fatal CHD during 6 years of follow-up. The cases were matched 1:2 with non-cases on age, smoking, and month of blood draw. We found both adhesion molecules directly associated with BMI, inflammatory biomarkers, and triglycerides and inversely associated with high-density lipoprotein and alcohol intake (p < 0.05). After adjustment for C-reactive protein, cholesterol-to-high-density lipoprotein ratio, age, smoking, BMI, physical activity, alcohol intake, history of diabetes, parental history of CHD, aspirin use, antihypertensive drug use, and fasting status, the relative risk of CHD was 1.69 [95% confidence interval (CI), 1.14 to 2.51] for sICAM-1 and 1.34 (95% CI, 0.91 to 1.96) for sVCAM-1, when comparing the top quintile with the lower four quintiles. Control for other inflammatory or lipid biomarkers did not appreciably attenuate the associations. When we cross-classified participants based on their sICAM-1 and sVCAM-1 levels, only the men in the top quintile of both biomarkers [relative risk = 2.39 (95% CI, 1.45 to 3.91)] had a significantly elevated risk of CHD (P interaction = 0.01, multivariate model). DISCUSSION: sICAM-1 and sVCAM-1 are directly associated with obesity and other CHD risk factors. The combination of high levels of both adhesion molecules might be associated with the development of CHD, independent of other CHD risk factors.

Aged↗
PubMed2000

Cell-cell adhesion-mediated tyrosine phosphorylation of nectin-2delta, an immunoglobulin-like cell adhesion molecule at adherens junctions.

We have recently found a novel functional unit of cell-cell adhesion at cadherin-based adherens junctions, consisting of at least nectin, an immunoglobulin-like cell adhesion molecule, and afadin, an actin filament-binding protein which connects nectin to the actin cytoskeleton. Among the members of the nectin family, we have found here that nectin-2delta is tyrosine-phosphorylated in response to cell-cell adhesion. Expression of E-cadherin induced tyrosine phosphorylation of nectin-2delta, while disruption of cell-cell adhesion by an anti-E-cadherin antibody reduced the tyrosine phosphorylation of nectin-2delta. An inhibitor specific for Src family kinase or expression of Csk reduced tyrosine phosphorylation of nectin-2delta. In addition, Src kinase tyrosine phosphorylates the recombinant cytoplasmic region of nectin-2delta in vitro. The major tyrosine phosphorylation site of nectin-2delta was Tyr505 in the cytoplasmic region, because the mutant nectin-2delta, of which Tyr505 was replaced by Phe, showed a loss of tyrosine phosphorylation in vivo and in vitro. These results, together with our recent observations, indicate that the cadherin-catenin system and the nectin-afadin system are closely connected to each other. The cadherin-mediated cell-cell adhesion system may link to the activation of a Src family kinase, that is, at least in part, responsible for the tyrosine phosphorylation of the cytoplasmic region of nectin-2delta. Oncogene (2000) 19, 4022 - 4028.

Animals↗