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Query: UNIPROT:P06889 (Mol)
 630,302 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

It is still largely unclear how cell adhesion molecule (CAM)-mediated signaling evokes responses from the growth cone cytoskeleton. Here we used TX-114 extraction of growth cones followed by equilibrium gradient centrifugation to isolate subfractions of detergent-resistant microdomains (DRMs) that could be structurally and functionally distinguished on the basis of localization and activation of components of CAM-mediated signaling pathways. DRMs enriched in cholesterol, caveolin, NCAM140, GPI-linked NCAM120, fyn, and GAP-43, all conventional markers of microdomains or rafts, were located in areas 2 and 3 of the gradient. Coimmunoprecipitation of specific components of CAM signaling pathways by GAP-43 then identified distinct subpopulations of DRMs. GAP-43 from area 2 DRMs coprecipitated GPI-linked NCAM120 and was inactive, i.e., PKC phosphorylation had not been stimulated. In contrast the GAP-43 from area 3 DRMs coprecipitated both transmembrane NCAM140 and caveolin and was active, i.e., highly phosphorylated by PKC. A different subset of DRMs from both area 2 and area 3 contained fyn that could not be coprecipitated with GAP-43 antibodies. In this case area 2 DRMs contained activated fyn that was phosphorylated on Y415. In contrast area 3 DRMs contained inactive fyn. Hence fyn and GAP-43, both targets of NCAM signaling, are located in distinct populations of DRMs, and their activated forms are reciprocally distributed on the gradient. A detergent-resistant membrane fraction recovered from area 4 was enriched in NCAM140, phosphorylated GAP-43, and actin, but not cholesterol, caveolin, or fyn. Immunoelectron microscopy revealed that phosphorylated GAP-43 was localized where the membranes and F-actin interacted. Our results provide evidence for NCAM-mediated signaling in DRMs and suggest that the DRMs responsible for fyn and PKC/GAP-43-mediated NCAM signaling are structurally distinct and differentially distributed in growth cones.
Mol Cell Neurosci 2002 Jan
PMID:Isolation and characterization of detergent-resistant microdomains responsive to NCAM-mediated signaling from growth cones. 1181 95

Since its first description the polysialylated form of NCAM (PSA-NCAM) is thought to be a major regulator of cell-cell interactions in the nervous system. Over the past few years many crucial questions have been answered concerning PSA biosynthesis and function. Among these are the identification and cloning of the key enzymes that are responsible for its synthesis and the fact that expression of PSA is not restricted to developmental stages but maintained in the adult nervous system. In the adult, PSA has been shown to be not only a marker of structural plasticity but seems to be a major player in these processes. Originally suggested to be a purely anti-adhesive factor, modulating cell-cell interactions in general and by this allowing plasticity, there is now increasing evidence that this might not be the whole story. Instead, it appears possible that PSA-NCAM interacts with secreted signaling molecules and by this fulfills a more instructive function in brain plasticity.
Mol Neurobiol
PMID:Revisiting the function of PSA-NCAM in the nervous system. 1183 54

Using the model of lysolecithin-induced demyelination of the corpus callosum in wild-type, NCAM-deficient, and endoneuraminidase-injected mice, we have analyzed the consequences of the loss of expression of NCAM or PSA residues on the migration and proliferation capacities of neural precursors of the subventricular zone (SVZ). We showed that the absence of PSA or NCAM delayed migration of neural precursors to the olfactory bulb and consequently enhanced their recruitment at the lesion site. Moreover, after demyelination, the lack of NCAM but not PSA promoted proliferation in the SVZ and the lesion while the lack of PSA favored the differentiation of the traced cells into the oligodendroglial fate both in the SVZ and in the lesion. As previously demonstrated in vitro (L. Decker et al., 2000, Mol. Cell. Neurosci. 16, 422-439), these data illustrate the involvement of PSA and NCAM in neural precursor motility and differentiation in the normal and injured central nervous system, suggesting distinct roles for these two molecules under pathophysiological conditions.
Mol Cell Neurosci 2002 Feb
PMID:Loss of polysialic residues accelerates CNS neural precursor differentiation in pathological conditions. 1186 Feb 75

The uterus contains all the components of a tertiary lymphoid compartment. We hypothesize that specific leukocyte recruitment to the endometrium during the secretory phase of the menstrual cycle and early pregnancy limits the type of immunocyte that gains access. The present study utilized flow cytometry to define and quantify adhesion molecules possibly used by decidual infiltrating lymphocytes (DIL) as homing receptors, uterine microvascular myometrial endothelial cells (UtMVE-Myo) as addressins, and secretory endometrial stroma cells (STO) as retainment factors. Human umbilical cord vein endothelial cells and peripheral blood lymphocytes were used as control cells for comparison studies. DIL were composed of predominantly lymphocyte function-associated antigen (LFA)-1+, intercellular adhesion molecule (ICAM)-1+, LFA-2+, LFA-3+, gp150,95+, alpha1beta1+, Hermes cell adhesion molecule (H-CAM)+, and neural cell adhesion molecule (N-CAM)+ (CD56(bright)) memory/effector natural killer cells. A significant number of UtMVEC-Myo expressed platelet endothelial cell adhesion molecule (PECAM)-1, a percentage were uniquely LFA-3+, and alpha4 integrin expression was uniquely high. An increased number of STO uniquely expressed alpha3, beta3, and LFA-3, whereas alpha2, alpha4, alphaVbeta3, and H-CAM were significantly increased. Possible unique adhesions of DIL:UtMVEC-Myo included SLe(x):PECAM, vascular cell adhesion molecule-1:alpha4, and LFA-2:LFA-3, whereas DIL:STO included LFA-2:LFA-3 and N-CAM:N-CAM. Unique molecules on DIL may also associate with extracellular matrix (ECM) or complement on UtMVEC-Myo or STO to form gp150,95:fibrinogen/iC3b/C3dg, alpha1beta1:laminin (LM)/collagen (CO), and ICAM-1:fibronectin (FN) interactions. Bridges of ECM may also form between DIL and UtMVEC-Myo adhesion molecules including ICAM-1:FN:ICAM-1 and alpha4beta1:FN:alpha4beta1. DIL:ECM:STO interactions may involve alpha2beta1:CO:alpha2beta1, alpha3beta1:LM/CO/FN:alpha3beta1, alphaVbeta3:VN:alphaVbeta3, and H-CAM:hyaluronate:H-CAM. It is likely that many adhesion molecules play a role in the recruitment and retainment of specialized lymphocytes within the uterine microenvironment. (Mackay et al., 1990).
Exp Mol Pathol 2002 Apr
PMID:Quantitative analysis of adhesion molecules on cellular constituents of the human uterine microenvironment under the influence of estrogen and progesterone. 1189 Jul 19

Hydroa-like cutaneous T-cell lymphoma (hydroa-like CTCL) is an unusual pediatric malignancy with a poor prognosis. An impressive cutaneous rash characterized by edema, blisters, ulcers, crusts, and scars, resembling hidroa vacciniforme, is seen mainly on the face and sometimes on the extremities. The lesion consists of lymphomatous T-cell infiltration of the skin and subcutis with variable exocytosis and angiocentricity. It has been also called edematous, scarring vasculitic panniculitis and hydroa-like lymphoma. An association with Epstein-Barr virus has been suggested. The differential diagnosis includes other cutaneous lymphomas, particularly the cutaneous nasal type T/natural killer-cell lymphoma, mycosis fungoides, precursor T-cell lymphoblastic lymphoma, nonspecific peripheral T-cell lymphoma, cutaneous anaplastic large cell lymphoma, and subcutaneous panniculitic T-cell lymphoma. Other differential diagnoses are inflammatory dermatopathies and panniculitides. Based on a series of 16 such cases referred to the Institute of Neoplastic Diseases, the objective of this report is not only to provide a better clinicopathologic understanding of this entity but also a reappraisal of it as a malignancy. The male/female frequency ratio was 1:1. The median age was 10 years old. All cases showed predominant facial involvement with edema, blisters, ulcers, crusts, and scars. Chemotherapy and/or radiotherapy had little or no benefit. The prognosis was usually dismal. The lymphoma extended from the epidermis to the subcutis, with frequent angiocentric and periadnexal array. Lymphoma cells were mostly of intermediate size with dense hyperchromatic nuclei, inconspicuous nucleoli, and infrequent mitosis. A scanty and variable inflammatory background was found. The lymphoma cells displayed T-cell cytotoxic phenotype. In addition, they were negative for the natural killer cell antigens CD56 and CD57. Epstein-Barr virus in situ hybridization was positive in the six cases in which it was assayed. T-cell receptor gamma (TCRgamma) displayed monoclonal-type rearrangement in four cases studied. Our findings indicate that hydroa-like CTCL is an independent clinicopathologic entity that affects children. Consequently, it should be considered an independent subset of CTCLs and be included as such in the classification of neoplastic diseases of the lymphoid tissues.
Appl Immunohistochem Mol Morphol 2002 Mar
PMID:Hydroa-like cutaneous T-cell lymphoma: a clinicopathologic and molecular genetic study of 16 pediatric cases from Peru. 1189 40

We have examined the effects of transforming growth factor beta1 (TGFbeta1) on gene expression in cultured rat Schwann cells (SCs). TGFbeta1 decreased the steady-state mRNA levels of several genes that are expressed by myelinating SCs but had varied effects on the mRNA levels of NCAM, L1, GAP-43, and p75-genes that are expressed by denervated and nonmyelinating SCs. TGFbeta1 antagonized the effects of forskolin on the mRNA levels of the transcription factors Oct-6/tst-1/SCIP and Krox20. Transcriptional run-off analysis demonstrated that the effects of TGFbeta1 on gene expression occur at least in part at the level of transcription. Thus, TGFbeta1 suppresses the expression of genes that characterize the different phenotypes of SCs, and these changes occur at least in part at a transcriptional level.
Mol Cell Neurosci 2002 Mar
PMID:TGFbeta1 modulates the phenotype of Schwann cells at the transcriptional level. 1190 5

Tissue repair is driven by migratory macrophages and fibroblasts that infiltrate injury sites and secrete growth factors. We now report the enhancement of skeletal muscle repair by targeting transgene delivery to these repair cells using matrix-immobilized gene vectors. Plasmid and adenovirus vectors immobilized in collagen-gelatin admixtures were delivered to excisional muscle wounds, and when encoding either fibroblast growth factor-2 (FGF2) or FGF6 transgenes, produced early angiogenic responses that subsequently remodeled into arteriogenesis. FGF2 gene delivery enhanced the number of CD31(+) endothelial cells present at treatment sites > 6-fold by day 14, and muscular arteriole density up to 11-fold by day 21 (P<0.0001). Muscle repair was also enhanced, as FGF gene-treated wounds filled with regenerating myotubes expressing the marker CD56 (an average 20-fold increase in CD56 expression versus controls, P<0.0001). These responses required transfection of a threshold level of repair cells, achievable only in injured muscles, and were transgene-driven, as neither platelet-derived growth factor-B (PDGFB) gene nor FGF2 protein delivery produced equivalent responses. In conclusion, using biomatrices to direct gene delivery to repair cells allows for relatively complex regenerative processes such as arteriogenesis and myogenesis, and therefore represents a promising approach to treating injured and ischemic muscle.
Mol Ther 2002 May
PMID:Delivery of FGF genes to wound repair cells enhances arteriogenesis and myogenesis in skeletal muscle. 1199 42

CD56+ NK/T cell lymphoma (NKTL) frequently involves skin and subcutaneous tissue. The characteristics of primary cutaneous nasal-type CD56+ NKTLs and secondary cutaneous involvement of nasal CD56+ NKTLs have not been clearly separated. This retrospective study analyzed 15 cases of NKTL (10 primary CD56+ NKTLs and 5 secondary CD56+ NKTLs) for their clinicopathologic and immunophenotypic characteristics using CD3, CD4, CD20, CD45RO, CD56, TIA-1, CD30, and Ki-67 antigens. In situ hybridization for Epstein-Barr virus RNA (EBERISH) and PCR for T cell receptor (TCR) gamma gene rearrangement were also performed. Clinically, NKTL-P was seen with equal frequency among male (five cases) and female (five cases) patients and presented with subcutaneous nodules without epidermal changes (nine cases), whereas all cases of NKTL-S occurred in male patients and presented with nodules or plaques with distinct epidermal changes (five cases). Microscopically, initial NKTL-P lesions had the panniculitic patterns of small to medium-sized cells (nine cases). NKTL-S lesions were extensive in both subcutis and dermis, with larger and more pleomorphic tumor cells (four cases) that also showed signs epidermotropism (five cases). In initial biopsies of CD56+ NKTL-P, a minority of tumor cells showed signals for EBERISH and in biopsies of CD56+ NKTL-S, virtually every tumor cell showed signals. While all five patients with secondary CD56+ NKTL died of disease with widespread systemic involvement within 16 months after onset of skin lesions, 7 out of the 10 primary CD56+ NKTL patients survived more than 20 months after onset of skin lesions, with slow progression and episodic recurrences. The primary and secondary cutaneous CD56+ NKTLs showed considerable clinicopathologic differences, suggesting differences in pathogenesis.
Appl Immunohistochem Mol Morphol 2002 Jun
PMID:Comparison of primary and secondary cutaneous CD56+ NK/T cell lymphomas. 1205 36

To define a dynamic sequence of phenotypic changes related to early and late phases of NK-cell activation, we have analyzed by four-color flow cytometry the immunophenotype of normal blood NK-cells from 12 healthy individuals and compared it with those from 15 patients with acute viral infections and 15 patients with either chronic infections or tumors. Although a great interindividual variability was found, nonstimulated CD56(+) NK-cells, present in normal blood samples, usually were CD2(-/+lo), CD7(+hi), HLA-DR(-), CD11b(+), CD38(+), CD11a(+hi), CD45RA(+hi), and CD45RO(-), the expression of CD11c and CD57 being heterogeneous and variable. Recently activated NK-cells, herein corresponding to NK-cells from patients with acute viral infections, displayed a pattern of expression of CD2/CD7 similar to that referred to above, but they typically showed higher levels of CD11a, CD38, and HLA-DR, as well as downregulation of CD11b and CD45RA, accompanied in some cases by coexpression of CD45RO; in addition, these NK-cells were CD11c(+) and CD57(-/+lo). Late-activated NK-cells, represented by NK-cells present in patients with chronic infections and tumors, converted into a CD2(+hi)/CD7(-/+lo) immunophenotype and expressed heterogeneously low levels of CD38 and CD11b; moreover, they were CD57(+) and CD11c(-/+). At this stage, most NK-cells had already reverted into their original CD45RA(+)/CD45RO(-)/HLA-DR(-) phenotype. In summary, we show that the patterns of expression of CD2/CD7, CD57/CD11c, CD38/CD11b, CD45RA/CD45RO, and CD11a/HLA-DR may help us to define the immunophenotypic profiles associated with early and late NK-cell activation phases in 'in vivo' models.
Blood Cells Mol Dis
PMID:The "ex vivo" patterns of CD2/CD7, CD57/CD11c, CD38/CD11b, CD45RA/CD45RO, and CD11a/HLA-DR expression identify acute/early and chronic/late NK-cell activation states. 1206 14

c-Jun, a crucial component of the dimeric transcription factor activating protein 1 (AP-1), can regulate apoptosis induced by oxidative stress and has been implicated in neuronal differentiation, but the mechanisms are largely unknown. We found that specific inhibition of transcription or stable transfection with cDNA encoding dominant-negative c-Jun sensitized SH-SY5Y neuroblastoma cells (TAM-67 cells) to apoptosis induced by the nitric oxide (NO) donor sodium nitroprusside or SIN-1. TAM-67 cells also became refractory to nerve growth factor (NGF)-induced neuronal differentiation. Dominant-negative c-Jun abolished expression of a 140-kDa neural cell adhesion molecule (NCAM140) and dramatically enhanced the expression of NCAM180 in TAM-67 cells. Inhibition of c-Jun in TAM-67 cells also resulted in a corresponding decrease in the amount of NCAM140 mRNA and an increase in the amount of NCAM180 mRNA. Reexpression of NCAM140 in TAM-67 cells restored NGF-induced neuronal differentiation and resistance to NO-induced apoptosis. Our results show that c-Jun/AP-1, through up-regulation of NCAM140, plays an important role in both NGF-induced neuronal differentiation and resistance to apoptosis induced by NO in neuroblastoma cells. As NCAM140 and NCAM180 are translated from differentially spliced mRNAs transcribed from the same gene, alternative splicing of NCAM pre-mRNA (and consequently the synthesis of the smaller NCAM140 species) appears to be regulated by c-Jun/AP-1.
Mol Cell Biol 2002 Aug
PMID:Neuronal differentiation and protection from nitric oxide-induced apoptosis require c-Jun-dependent expression of NCAM140. 1210 Dec 31


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