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

We have begun to explore the downstream signaling pathways of receptor protein tyrosine phosphatases (RPTPs) that control axon guidance decisions in the Drosophila central nervous system. We have focused our studies on the adhesion molecule-like gp150 protein, which binds directly to and is an in vitro substrate for the RPTP DPTP10D. Here we show that gp150 and DPTP10D form stable complexes in Drosophila Schneider 2 (S2) cells and in wild-type larval tissue. We also demonstrate that the DPTP10D cytoplasmic domain is sufficient to confer binding to gp150. gp150 has a short cytoplasmic domain containing four tyrosines, all found within sequences similar to immunoreceptor family tyrosine-based activation motifs (ITAMs). We demonstrate that gp150 is tyrosine phosphorylated in wild-type larvae. In S2 cells, gp150 becomes tyrosine phosphorylated following incubation with PTP inhibitors or upon coexpression of the Dsrc tyrosine kinase. Phosphorylated Dsrc and an unknown 40-kDa phosphoprotein form stable complexes with gp150, thereby implicating them in a putative gp150 signaling pathway. When coexpressed with gp150, either full-length DPTP10D or its cytoplasmic domain mediates gp150 dephosphorylation whereas a catalytically inactive DPTP10D cytoplasmic domain does not. The neural RPTP DPTP99A can also induce gp150 dephosphorylation but does not coimmunoprecipitate with gp150. Taken together, the results suggest that gp150 transduces signals via phosphorylation of its ITAM-like elements. Phosphotyrosines on gp150 might function as binding sites for downstream signaling molecules, thereby initiating a signaling cascade that could be modulated in vivo by RPTPs such as DPTP10D.
Mol Cell Biol 1997 Dec
PMID:Transmembrane glycoprotein gp150 is a substrate for receptor tyrosine phosphatase DPTP10D in Drosophila cells. 937 17

Redox stress during post-ischemic reperfusion may be the prime signal for processes leading to myocardial remodelling and hypertrophy. Nitric oxide (NO) is antioxidative, antiadhesive for neutrophils (PMN) and antiproliferative. Thus, enhancing endothelial production of NO, e.g. by inhibiting breakdown of endogenous bradykinin via angiotensin converting enzyme (ACE), could be beneficial. The effect of cilazaprilat (CILA, 10 micro M), an ACE inhibitor, on redox status, expression of the adhesion molecule P-selectin, and PMN adhesion under conditions of oxidative stress was investigated in cultured human umbilical vein endothelial cells (HUVECs). Incubation of the cells with H2O2 (0.1 and 1 mm) for 15 min served as oxidative stimulus. The intra- and extracellular concentrations of reduced and oxidized glutathione (GSH and GSSG) were measured by HPLC as indicators of endothelial redox status. Expression of P-selectin was measured by flow cytometry. Furthermore, firm leukocyte adhesion to HUVECs was assessed. In controls, the intracellular ratio GSH/GSSG averaged 47 and dropped to 30 after incubation with 0.1 mm H2O2. The ratio declined to 6.5 with 1 mm H2O2. CILA blocked the effects of 0.1 mm H2O2, but was ineffective against 1 mm peroxide. The extracellular ratio did not discriminate between 0.1 and 1 mm H2O2, falling from 18 to 1 in both situations. P-selectin expression rose from 100% (control) to 146% after 1 mm H2O2 without CILA, but only to 114% in the presence of CILA. PMN adhesion was enhanced from about 1600 PMN per microwell (control) to 4300/well by 1 mm H2O2. CILA had no significant effect on adhesion (3900 PMN/well). Exposure of HUVECs to 0.1 mm H2O2 affected neither P-selectin expression nor PMN adhesion. Consequently, ACE inhibition can mitigate mild (0.1 mm H2O2) but not more severe redox stress in HUVECs. Irrespectively, CILA reduced the upregulation of P-selectin at the higher H2O2 concentration, indicating that this process is regulated independently of the cellular redox status. The firm adhesion of PMN to HUVECs was independent of P-selectin expression.
J Mol Cell Cardiol 1997 Nov
PMID:Effects of ACE-inhibition on redox status and expression of P-selectin of endothelial cells subjected to oxidative stress. 940 70

Adhesion molecule expression by pulmonary endothelial cells is considered to play an important role in the recruitment of circulating leukocytes to sites of inflammation in the lung. We have used P-selectin- and intercellular adhesion molecule type 1 (ICAM-1)-deficient mice to determine whether these adhesion molecules are important to pulmonary eosinophil recruitment after allergen challenge. There was a significant inhibition of lung tissue eosinophil recruitment in ICAM-1-deficient mice (approximately 84% inhibition compared to wild-type mice) and P-selectin-deficient mice (approximately 67% inhibition compared to wild-type mice) 3 h after allergen challenge. The number of bronchoalveolar lavage (BAL) eosinophils in P-selectin-deficient and ICAM-1-deficient mice was also significantly reduced compared with wild-type mice. Levels of BAL eosinophil peroxidase (EPO) were significantly lower in ICAM-1-deficient mice (0.21 +/- 0.03 EPO units) compared with wild-type mice (3.34 +/- 0.65 EPO units). There was no significant difference in the degree of inhibition of eosinophil recruitment in ICAM-1-deficient mice at the three time points (3, 12, and 24 h) of study after allergen challenge. However, in P-selectin-deficient mice there was a decline in the degree of inhibition of eosinophil recruitment from 3 h (67% inhibition) and 12 h (72% inhibition) postchallenge, to 24 h postchallenge (38% inhibition), suggesting that other adhesion molecules may be playing a more prominent role than P-selectin at later time points. These studies suggest an important role for ICAM-1 and P-selectin in eosinophil recruitment to the lung after allergen challenge.
Am J Respir Cell Mol Biol 1998 Feb
PMID:Inhibition of pulmonary eosinophilia in P-selectin- and ICAM-1-deficient mice. 947 9

A study of the effect of the L-3,5,3'-triiodothyronine hormone on the expression of the mRNA of the adhesion molecule ICAM-1 led to the observation that the mRNA level is slightly up-regulated in human umbilical-cord endothelial cells. To analyze this induction at a molecular level, the search of T3 hormone receptors was undertaken. In this paper, we show that ECV 304 endothelial cells express the mRNAs encoding two thyroid hormone receptor isoforms alpha(alpha1 and alpha2) and one beta(beta1). This is, to our knowledge, a first important step towards the demonstration of the involvement of these receptors in the induction of the expression of ICAM-1 by the T3 hormone.
Cell Mol Biol (Noisy-le-grand) 1997 Dec
PMID:Expression of thyroid hormone receptors alpha and beta-1 messenger RNAs in human endothelial cells. The T3 hormone stimulates the synthesis of the messenger RNA of the intercellular adhesion molecule-1. 948 46

bEND.3 cells are polyoma middle T-transformed mouse brain endothelial cells that express very little or no thrombospondin-1, a natural inhibitor of angiogenesis, but express high levels of platelet endothelial cell adhesion molecule-1 (PECAM-1) that localizes to sites of cell-cell contact. Here, we have examined the role of PECAM-1 in regulation of bEND.3 cell proliferation, migration, morphogenesis, and hemangioma formation. We show that down-regulating PECAM-1 expression by antisense transfection of bEND. 3 cells has a dramatic effect on their morphology, proliferation, and morphogenesis on Matrigel. There is an optimal level for PECAM-1 expression such that high levels of PECAM-1 inhibit, whereas moderate levels of PECAM-1 stimulate, endothelial cell morphogenesis. The down-regulation of PECAM-1 in bEND.3 cells resulted in reexpression of endogenous thrombospondin-1 and its antiangiogenic receptor CD36. The expression of the vascular endothelial growth factor receptors flk-1 and flt-1, as well as integrins and metalloproteinases (which are involved in angiogenesis), were also affected. These observations are consistent with the changes observed in proliferation, migration, and adhesion characteristics of the antisense-transfected bEND.3 cells as well as with their lack of ability to form hemangiomas in mice. Thus, a reciprocal relationship exists between thrombospondin-1 and PECAM-1 expression, such that these two molecules appear to be constituents of a "switch" that regulates in concert many components of the angiogenic and differentiated phenotypes of endothelial cells.
Mol Biol Cell 1998 Apr
PMID:Down-regulation of platelet endothelial cell adhesion molecule-1 results in thrombospondin-1 expression and concerted regulation of endothelial cell phenotype. 952 72

P84 is a novel neural adhesion molecule that may play an important role in synaptogenesis. We have recently cloned a murine cDNA encoding the P84 adhesion molecule. The human homologue of P84 has previously been isolated (by others) as a brain specific cDNA containing CCA repeats. We have mapped the human P84 gene to the subtelomeric region of chromosome 20p (20p13) by FISH. In addition, we have been able to place P84 onto the high resolution physical map of the human genome by utilizing the Unigene database. P84 maps to several YAC clones, between STS markers IB255 and WI-9632, and very close to the polymorphic marker D20S199, in an interval of less than 1 Mb on 20p13. P84 is a strong candidate gene for neurological disorders which map into this region.
Somat Cell Mol Genet 1997 Jul
PMID:Mapping of the human P84 gene to the subtelomeric region of chromosome 20p. 954 32

Evidence suggests that cellular adhesion is critical for eosinophil effector functions. Here, we tested the hypothesis that an adhesion molecule, specifically beta2 integrin, participates in intracellular signaling events of eosinophils. Eosinophils stimulated with interleukin (IL)-5 and adherent to protein-coated tissue culture plates via beta2 integrin (CD18) showed tyrosine phosphorylation of a number of proteins. Among these proteins, tyrosine phosphorylation of the 105 kD and 115 kD proteins and the product of the c-cbl protooncogene, Cbl, was specifically inhibited using soluble anti-CD18 monoclonal antibody (mAb) to block eosinophil cell adhesion. Furthermore, phosphoinositide turnover of IL-5-stimulated adherent eosinophils was also inhibited by anti-CD18 mAb, suggesting that cellular adhesion plays important roles in eosinophil signal transduction. alphaM beta2 (Mac-1, CD11b/18) was one of the beta2 integrins involved in eosinophil adhesion to protein-coated plates. We found that direct ligation of eosinophil alphaM beta2 with anti-CD11b mAb coupled to polystyrene microbeads induced tyrosine phosphorylation of a 115 kD protein and Cbl. Furthermore, anti-CD11b mAb microbeads induced increases in both phosphoinositide hydrolysis and the eosinophil degranulation response. Control antibodies, such as mouse myeloma IgG1 and anti-HLA class I antigen mAb, did not induce these cellular responses. These results suggest that engagement of beta2 integrin either by cell adhesion or by anti-CD11b mAb triggers activation of an intracellular signaling cascade, including protein tyrosine phosphorylation and phosphoinositide turnover, and subsequent cellular degranulation in human eosinophils. Tyrosine phosphorylation of a 115 kD protein and Cbl may play important roles in adhesion-dependent cellular functions of eosinophils.
Am J Respir Cell Mol Biol 1998 May
PMID:Ligation of the beta2 integrin triggers activation and degranulation of human eosinophils. 956 38

With the aim to analyze the ontogeny of the mouse endothelium, monoclonal antibody (mAb) MEC 13.3 was used for the immunohistochemical staining of frozen sections of different stages of mouse embryo development. This mAb specifically recognizes membrane reinforcement of endothelial cells (EC) from mouse blood vessels, indicating the expression of a molecule related to the murine form of PECAM-1/CD31. The present study reports the expression of the murine PECAM-1/CD31 antigen, observed with the peroxidase-antiperoxidase technique, in a single cell type, with a typical non-differentiated morphology at an early stage of mouse postimplantation embryos. A progressive increase in the number of this cell type was observed in the early stages of murine development, but few were detected at mature stages. On the other hand, EC in days 9.5, 14.5 and 19.5 postcoitum embryos were also recognized by the same mAb MEC 13.3 allowing the recognition of a cell type related directly or indirectly to vascular network development.
Cell Mol Biol (Noisy-le-grand) 1998 May
PMID:Platelet endothelial cell adhesion molecule-1 expression during mouse postimplantation development. 962 Apr 51

P-selectin is an adhesion molecule, expressed at the surface of activated cells, that mediates the interaction of activated endothelial cells or platelets with leukocytes. P-selectin expression is increased in atherosclerotic plaques, and high plasma levels of this molecule have been observed in patients with unstable angina. We investigated the P-selectin gene as a possible candidate for myocardial infarction (MI). The P-selectin gene is situated on chromosome 1q21-q24, spans >50 kb and contains 17 exons. The sequences of the 5'-flanking region and exons of 40 alleles from patients with MI were screened for polymorphisms using polymerase chain reaction/single-strand conformation polymorphism (PCR-SSCP) and sequencing. Thirteen polymorphisms were identified: five in the 5'-flanking and eight in the exonic sequences. Four polymorphisms (Ser290Asn, Asn562Asp, Leu599Val and Thr715Pro) predicted a change in the amino acid sequence of the P-selectin protein. All P-selectin polymorphisms as well as a common E-selectin polymorphism, Ser128Arg which has been reported as being associated with an increased risk of premature coronary heart disease (CHD), and is in tight linkage disequilibrium with several P-selectin polymorphisms, were investigated in 647 patients with MI and 758 control subjects from four regions of France and Northern Ireland (the ECTIM study). The entire set of P-selectin polymorphisms provided a heterozygosity of 91%. The polymorphisms were tightly associated with one another and displayed patterns of linkage disequilibrium suggesting the existence of highly conserved ancestral haplotypes. The five polymorphisms in the 5'-flanking region of the gene were unrelated to MI or any relevant phenotype measured in the ECTIM study. We inferred that the four missense variants identified in the coding region predicted eight common forms of the P-selectin protein. The Pro715 allele which characterizes one of these forms was less frequent in France than in Northern Ireland ( P < 0.002) and in cases than in controls ( P < 0.002; P < 0.02 after correction for the number of tests). We conclude that the P-selectin gene is highly polymorphic and hypothesize that the Pro715 variant may be protective for MI. Whether this variant affects the properties of the P-selectin protein in a way which is compatible with this hypothesis needs to be checked experimentally.
Hum Mol Genet 1998 Aug
PMID:The P-selectin gene is highly polymorphic: reduced frequency of the Pro715 allele carriers in patients with myocardial infarction. 966 70

1. It is presently widely assumed that structural reorganization of synaptic architectures subserves the functional gains that define certain neuronal plasticities. 2. While target molecules thought to participate in such morphological dynamics are not well defined, growing evidence suggests a pivotal role for cell adhesion molecules. 3. Herein, brief discussions are presented on (i) the history of how adhesion molecules became implicated in plasticity and memory processes, (ii) the general biology of some of the major classes of such molecules, and (iii) the future of the adhesion molecule/plasticity relationship.
Cell Mol Neurobiol 1998 Oct
PMID:The relationship between adhesion molecules and neuronal plasticity. 977 47


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