Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P06889 (Mol)
 630,302 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Neurite growth and guidance depends on the transduction of extracellular guidance cues into motile responses by the sensory apparatus at the tip of the neurite, the growth cone. Contact of the growth cone with extracellular ligands leads to the cytoskeletal reorganisation required for changes in rate of motility and direction of outgrowth. Differential adhesion mediated by cell adhesion molecules and signal transduction pathways mediated by growth cone receptors were once seen as separate but cooperative events in controlling growth cone motility. However, recent findings suggest that cell adhesion molecules can activate novel signalling pathways in the growth cone by the recruitment of fibroblast growth factor receptors leading to neurite outgrowth. This Review focuses on work by various laboratories centering on the intracellular consequences of the cell adhesion molecule-mediated activation of the fibroblast growth factor receptor. These include activation of a lipase cascade including phospholipase C and diacylglycerol lipase and culminating in the release of arachidonic acid. This release of arachidonic acid is proposed to activate the transient opening of voltage dependent ion-channels leading to localised rises in growth Ca(2+). Recent findings demonstrating this previously undetectable rise in Ca(2+) in the growth cone are discussed in light of the proposed roles and mechanisms of Ca(2+) in controlling neurite outgrowth. The Ca(2+) rises are thought to induce the activation of GAP43 and Ca(2+)/calmodulin-dependent kinase II, molecules implicated in the modulation of cytoskeletal remodelling. The evidence that this pathway may be involved in the guidance of retinal ganglion cells is evaluated.
Mol Cell Biol Res Commun 2000 May
PMID:The generation of localized calcium rises mediated by cell adhesion molecules and their role in neuronal growth cone motility. 1096 48

The carcinoembryonic antigen (CEA) family consists of a large group of evolutionarily divergent glycoproteins. The secreted pregnancy-specific glycoproteins constitute a subgroup within the CEA family. They are predominantly expressed in trophoblast cells throughout placental development and are essential for a positive outcome of pregnancy, possibly by protecting the semiallotypic fetus from the maternal immune system. The murine CEA gene family member CEA cell adhesion molecule 9 (Ceacam9) also exhibits a trophoblast-specific expression pattern. However, its mRNA is found only in certain populations of trophoblast giant cells during early stages of placental development. It is exceptionally well conserved in the rat (over 90% identity on the amino acid level) but is absent from humans. To determine its role during murine development, Ceacam9 was inactivated by homologous recombination. Ceacam9(-/-) mice on both BALB/c and 129/Sv backgrounds developed indistinguishably from heterozygous or wild-type littermates with respect to sex ratio, weight gain, and fertility. Furthermore, the placental morphology and the expression pattern of trophoblast marker genes in the placentae of Ceacam9(-/-) females exhibited no differences. Both backcross analyses and transfer of BALB/c Ceacam9(-/-) blastocysts into pseudopregnant C57BL/6 foster mothers indicated that Ceacam9 is not needed for the protection of the embryo in a semiallogeneic or allogeneic situation. Taken together, Ceacam9 is dispensable for murine placental and embryonic development despite being highly conserved within rodents.
Mol Cell Biol 2000 Oct
PMID:Trophoblast cell-specific carcinoembryonic antigen cell adhesion molecule 9 is not required for placental development or a positive outcome of allotypic pregnancies. 1098 30

Multidimensional, homo- and heteronuclear magnetic resonance spectroscopy combined with dynamical annealing has been used to determine the structure of a 94 residue module (X2 1) of the scaffolding protein CipC from the anaerobic bacterium Clostridium cellulolyticum. An experimental data set comprising 1647 nuclear Overhauser effect-derived restraints, 105 hydrogen bond restraints and 66 phi torsion angle restraints was used to calculate 20 converging final solutions. The calculated structures have an average rmsd about the mean structure of 0.55(+/-0.11) A for backbone atoms and 1.40(+/-0.11) A for all heavy atoms when fitted over the secondary structural elements. The X2 1 module has an immunoglobulin-like fold with two beta-sheets packed against each other. One sheet contains three strands, the second contains four strands. An additional strand is intercalated between the beta-sandwich, as well as two turns of a 3(.10) helix. X2 1 has a surprising conformational stability and may act as a conformational linker and solubility enhancer within the scaffolding protein. The fold of X2 1 is very similar to that of telokin, titin Ig domain, hemolin D2 domain, twitchin immunoglobulin domain and the first four domains of the IgSF portion of transmembrane cell adhesion molecule. As a consequence, the X2 1 module is the first prokaryotic member assigned to the I set of the immunoglobulin superfamily even though no sequence similarity with any member of this superfamily could be detected.
J Mol Biol 2000 Nov 24
PMID:Solution structure of the module X2 1 of unknown function of the cellulosomal scaffolding protein CipC of Clostridium cellulolyticum. 1108 Apr 56

Vascular cell adhesion molecule-1 (VCAM-1) is expressed in early stages of atherosclerosis; however, the mechanisms of its upregulation are not fully understood. In the present study, we examined the effects of interleukin-4 (IL-4) on VCAM-1 gene expression and its transcriptional regulatory mechanism in human umbilical vein endothelial cells (HUVEC). Reverse transcription-polymerase chain reaction showed that VCAM-1 mRNA was induced in IL-4-treated HUVEC in a time- and dose-dependent manner. Among known transcription factors that have binding sites in the promoter region of the VCAM-1 gene, IL-4 activated only SP-1. In contrast, nuclear factor- kappa B (NF- kappa B), activator protein-1 (AP-1) and interferon regulatory factor-1 (IRF-1), which also have consensus binding sequences in the 5'-flanking region of the human VCAM-1 gene, were not activated. The role of SP-1 in IL-4-induced VCAM-1 expression was confirmed in HUVEC transfected with a reporter construct of the VCAM-1 promoter with mutated SP-1 binding site. As IL-4 treatment of HUVEC enhanced the intracellular oxidizing potential, as indicated by an increase in 2',7'-dichlorofluorescein (DCF) fluorescence, we studied the effect of antioxidants on IL-4-induced VCAM-1 expression. Pretreatment of HUVEC with pyrrolidine dithiocarbamate (PDTC) or N-acetylcysteine (NAC) completely prevented IL-4-induced VCAM-1 expression. In addition, PDTC inhibited IL-4-related activation of SP-1. These results suggest that IL-4-induced oxidative stress upregulates the expression of VCAM-1 gene in HUVEC at transcriptional levels via activation of SP-1 transcription factor. In contrast, NF- kappa B, AP-1 or IRF-1 do not appear to be involved in the signal transduction cascade.
J Mol Cell Cardiol 2001 Jan
PMID:IL-4-induced oxidative stress upregulates VCAM-1 gene expression in human endothelial cells. 1113 25

The cell adhesion molecule E-cadherin has been implicated in maintaining the polarized phenotype of epithelial cells and suppression of invasiveness and motility of carcinoma cells. Na,K-ATPase, consisting of an alpha- and beta-subunit, maintains the sodium gradient across the plasma membrane. A functional relationship between E-cadherin and Na,K-ATPase has not previously been described. We present evidence that the Na,K-ATPase plays a crucial role in E-cadherin-mediated development of epithelial polarity, and suppression of invasiveness and motility of carcinoma cells. Moloney sarcoma virus-transformed Madin-Darby canine kidney cells (MSV-MDCK) have highly reduced levels of E-cadherin and beta(1)-subunit of Na,K-ATPase. Forced expression of E-cadherin in MSV-MDCK cells did not reestablish epithelial polarity or inhibit the invasiveness and motility of these cells. In contrast, expression of E-cadherin and Na,K-ATPase beta(1)-subunit induced epithelial polarization, including the formation of tight junctions and desmosomes, abolished invasiveness, and reduced cell motility in MSV-MDCK cells. Our results suggest that E-cadherin-mediated cell-cell adhesion requires the Na,K-ATPase beta-subunit's function to induce epithelial polarization and suppress invasiveness and motility of carcinoma cells. Involvement of the beta(1)-subunit of Na,K-ATPase in the polarized phenotype of epithelial cells reveals a novel link between the structural organization and vectorial ion transport function of epithelial cells.
Mol Biol Cell 2001 Feb
PMID:Na,K-ATPase beta-subunit is required for epithelial polarization, suppression of invasion, and cell motility. 1117 15

Altered expression of cell adhesion molecule expression has been implicated in a variety of chronic inflammatory conditions. Regulation of adhesion molecule expression by specific redox sensitive mechanisms has been reported. Grape seed proanthocyanidins have been reported to have potent antioxidant properties. We evaluated the effects of grape seed proanthocyanidin extract (GSPE) on the expression of TNFalpha-induced ICAM-1 and VCAM-1 expression in primary human umbilical vein endothelial cells (HUVEC). GSPE at low concentrations (1-5 micrograms/ml), down-regulated TNFalpha-induced VCAM-1 expression but not ICAM-1 expression in HUVEC. Such regulation of inducible VCAM-1 by GSPE was also observed at the mRNA expression level. A cell-cell co-culture assay was performed to verify whether the inhibitory effect of GSPE on the expression of VCAM-1 was also effective in down-regulating actual endothelial cell/leukocyte interaction. GSPE treatment significantly decreased TNFalpha-induced adherence of T-cells to HUVEC. Although several studies have postulated NF-kappaB as the molecular site where redox active substances act to regulate agonist-induced ICAM-1 and VCAM-1 gene expression, inhibition of inducible VCAM-1 gene expression by GSPE was not through a NF-kappaB-dependent pathway as detected by a NF-kappaB reporter assay. The potent inhibitory effect of low concentrations of GSPE on agonist-induced VCAM-1 expression suggests therapeutic potential of this extract in inflammatory conditions and other pathologies involving altered expression of VCAM- 1.
Mol Cell Biochem 2001 Jan
PMID:Regulation of inducible adhesion molecule expression in human endothelial cells by grape seed proanthocyanidin extract. 1121 53

Ep-CAM is a new type of cell adhesion molecule (CAM) which does not structurally resemble the members of the four major families (cadherins, integrins, selectins, and CAMs of the immunoglobulin superfamily) and mediates Ca(2+)-independent, homophilic adhesions. The extracellular domain of Ep-CAM consists of a cysteine-rich region, containing two type II epidermal growth factor (EGF)-like repeats, followed by a cysteine-poor region. We generated mutated Ep-CAM forms with various deletions in the extracellular domain. These deletion mutants, together with monoclonal antibodies recognizing different epitopes in the extracellular domain, were used to investigate the role of the EGF-like repeats in the formation of intercellular contacts mediated by Ep-CAM molecules. We established that both EGF-like repeats are required for the formation of Ep-CAM-mediated homophilic adhesions, including the accumulation of Ep-CAM molecules at the cell-cell boundaries, and the anchorage of the Ep-CAM adhesion complex to F-actin via alpha-actinin. Deletion of either EGF-like repeat was sufficient to inhibit the adhesion properties of the molecule. The first EGF-like repeat of Ep-CAM is required for reciprocal interactions between Ep-CAM molecules on adjacent cells, as was demonstrated with blocking antibodies. The second EGF-like repeat was mainly required for lateral interactions between Ep-CAM molecules. Lateral interactions between Ep-CAM molecules result in the formation of tetramers, which might be the first and necessary step in the formation of Ep-CAM-mediated intercellular contacts.
Mol Cell Biol 2001 Apr
PMID:Epidermal growth factor-like repeats mediate lateral and reciprocal interactions of Ep-CAM molecules in homophilic adhesions. 1125 4

We have analyzed the influence of the calcium-dependent cell adhesion molecule, N-cadherin, on events leading to CNS myelination. Interactions between axons and oligodendrocyte progenitor (OP) cells and the CG4 OP cell line were examined by video-microscopy. OPs cocultured with dorsal root ganglia explants migrated around the culture and formed numerous contacts with axons. The duration of these contacts depended on the morphology of the OP, with OPs containing four or more processes forming long-lasting contacts and OPs with three or fewer processes forming short-termed contacts. Treatment with N-cadherin function blocking peptides approximately halved the duration of contacts made by cells with four or more processes but contact times for cells with three or less processes were unaffected. The L7 cadherin-blocking antibody and calcium withdrawal had similar effects. Contacts with axons regenerating from explants of adult retina, which do not have N-cadherin on their surface was examined. The contact duration of OPs to adult retina axons was short and similar in length to those formed between OPs and dorsal root ganglion axons in the presence of cadherin blocking reagents. Oligodendrocyte myelination was examined in organotypic rat cerebellar slice cultures, taken before myelination at postnatal day 10 and then allowed to myelinate in vitro over 7 days. When incubated with an N-cadherin function-blocking peptide, myelination of Purkinje cell axons was reduced to about half of control levels, while control peptides were without effect. Cadherin-blockade did not prevent maturation of OPs, since oligodendrocytes showing myelin basic protein immunostaining were still found in these cultures. However, many of the cell processes did not colocalize with calbindin-positive axons. From these data we conclude that N-cadherin is important for the initial contact between a myelinating oligodendrocyte and axons and significantly contributes to the success of myelination.
Mol Cell Neurosci 2001 Jun
PMID:N-cadherin is involved in axon-oligodendrocyte contact and myelination. 1141 96

Beta-1,4-galactosyltransferase 1 (beta1,4-GT 1) is the key enzyme transferring galactose to the terminal N-acetylglucosamine (GlcNAc) forming Galbeta3-->4GlcNAc structure in the Golgi apparatus. In addition, it also serves as a cell adhesion molecule by recognizing and binding to terminal GlcNAc of glycoconjugates on the adjacent cell surface and matrix through a subpopulation of the enzyme distributed on the cell surface. Transient expression of the p58GTA protein kinase, which belongs to the p34cdc2-related supergene family, could enhance beta1,4-GT 1 total activity in COS cells. In this study, the p58GTA interaction with beta1,4-GT 1 was confirmed using an in vitro assay with the TNT Coupled Reticulocyte Lysate System. An expression vector containing p58GTA was stably transfected into 7721 cells, a human hepatocarcinoma cell line, expression was confirmed by Northern and Western blot analyses. The cells transfected with p58GTA (p58GTA/7721) contained 1.9 times higher total beta1,4-GT 1 activity and 2.6 times higher cell-surface beta1,4-GT 1 activity than the mock transfected cells (pcDNA3/7721). However, Ricinus communis agglutinin-I lectin blot analysis revealed that the enhanced beta1,4-GT1 activity did not increase the Galbetal-->4GlcNAc groups on most of the membrane proteins in p58GTA/7721 cells. By flow cytometry analysis, it was found that the p58GTA/7721 cells were G2/M phase arrested, compared with the pcDNA3/7721 cells. These results suggest that the p58GTA stable transfection into human hepatocarcinoma cells could enhance the two beta1,4-GT1 subcellular pool activities independently and change its cell-cycle without modifying the beta-1,4-linked galactose residues on most membrane proteins.
Mol Cell Biochem 2001 May
PMID:Effect of p58GTA on beta-1,4-galactosyltransferase 1 activity and cell-cycle in human hepatocarcinoma cells. 1150 80

Inactivating mutations have been found in the cell-cell adhesion molecule E-cadherin (CDH1), which acts as a tumor suppressor gene in different kinds of cancers, e.g. primarily diffuse gastric cancer and lobular breast cancer. In this study, we screened for germline alterations in familial gastric and colon cancer cases. In total, 20 gastric and 18 colon cancer patients with both familial gastric and colon cancer were tested for germline E-cadherin alterations by using PCR/SSCP, specific restriction digestion test and sequencing. No pathogenic mutations were identified in the gastric cancer patients. In two colon cancer patients, a missense mutation in exon 12, codon 592 (Ala592Thr) was found. This alteration segregated with diffuse gastric cancer and colon cancer in one of the families. The prevalence of this alteration in the general population and colon cancer cases was almost the same. However, the fact that this alteration (Ala592Thr) segregated with colon cancer and diffuse gastric cancer in one big family, suggests that this E-cadherin missense alteration, beside predisposing to diffuse gastric cancer, also may play a role in colorectal carcinogenesis.
Int J Mol Med 2001 Oct
PMID:A germline E-cadherin mutation in a family with gastric and colon cancer. 1156 85


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>