Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.1.4.3 (phospholipase C)
 18,461 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The aim of this study was to explore whether Thy-1, like other members of the Ig-like superfamily (e.g., CD2 and neural cell adhesion molecule), participates in cell-cell adhesion. This was investigated by measuring the binding of Thy-1+ probe cells (thymocytes or AKR1 T lymphoma cells) to Thy-1- cloned mouse thymic epithelial (MTE) cells using a quantitative cell adhesion assay. The results were as follows: (a) the thymo-epithelial cell interaction was found to be inhibitable (by 25-40%) by soluble Thy-1 molecules purified from phosphatidylinositol-specific phospholipase C-treated mouse thymocytes as well as by Fab' fragments of a Thy-1-specific mAb; (b) the binding of the Thy-1- AKR1 (Thy-1-d) mutant to MTE cells was found to be reduced (by 50%) as compared with that of the wild type T lymphoma; (c) the Thy-1-mediated adhesion pathway did not require Ca2+ and promoted the initial thymo-epithelial binding measured at 4 degrees C. These data provide the first direct evidence of an adhesive function of Thy-1 and suggest that this molecule, in addition to its T cell triggering properties, might play a role during the early T cell maturation by promoting thymocyte adhesion to thymic stroma.
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PMID:Thy-1 supports adhesion of mouse thymocytes to thymic epithelial cells through a Ca2(+)-independent mechanism. 167 Oct 83

The possible role of neural cell adhesion molecule (NCAM) in myelination was studied in the dysmyelinating mouse mutants jimpy and shiverer, by characterizing the expression of the different molecular forms of brain NCAM as a function of age. In jimpy, the expression of NCAM-120 (120,000-Da NCAM) was low and in shiverer both NCAM-120 and NCAM-180 (180,000-Da NCAM) were reduced when compared to controls. In both jimpy and shiverer there was no significant change in the phospholipase C-sensitive NCAM-120. These data further support the possibility that NCAM may be involved in myelination.
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PMID:Expression of neural cell adhesion molecule in dysmyelinating mutants. 229 27

The expression of the neural cell adhesion molecule (N-CAM) on cultured murine oligodendrocytes, their precursors, and myelin was examined by indirect immunofluorescence, biosynthetic radiolabeling followed by immunoprecipitation and Western blot analysis, using antibodies specific for various forms of the molecule. In all culture systems studied, whether the oligodendrocytes were cultured as an enriched fraction containing precursor cells or in the presence of astrocytes and neurons, a similar differentiation-stage-related expression of N-CAM was seen. At early developmental stages many tetanus toxin receptor- and A2B5 antigen-positive putative oligodendrocyte precursors with bipolar morphology were seen and found to express N-CAM in its embryonic form. Of the 04 antigen-positive immature oligodendrocytes with few slender processes most expressed N-CAM, but few the embryonic form of N-CAM. The more mature 01 or 010 antigen-positive oligodendrocytes were found to express exclusively the adult form of N-CAM. Oligodendrocytes synthesized the 120 and 140 kD forms of N-CAM (N-CAM 120 and N-CAM 140), but not N-CAM 180, although with differentiation, N-CAM 120 predominated in oligodendrocytes and also in pure myelin. N-CAM 120 could be released from oligodendrocytes and myelin by phosphatidylinositol-specific phospholipase C, suggesting that in both oligodendrocytes and myelin N-CAM 120 is inserted into the membrane by covalent linkage to phosphatidylinositol.
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PMID:Differentiation-regulated loss of the polysialylated embryonic form and expression of the different polypeptides of the neural cell adhesion molecule by cultured oligodendrocytes and myelin. 266 42

The neural cell adhesion molecule (N-CAM) is detected in chicken brain as three polypeptides of 180 kDa, 140 kDa, and 120 kDa that arise from a single gene by alternative splicing. Heart tissue, however, contains components of 150 kDa, 140 kDa, and 130 kDa; neither the differences in molecular mass among these components nor the difference between neural and cardiac N-CAM could be accounted for by variations in glycosylation alone. A cDNA clone isolated from an embryonic chicken heart library, [lambda N101B, 1.8 kilobases (kb)] contained a 93-base-pair (bp) insert not found in neural N-CAM cDNAs. In the N-CAM gene this sequence mapped within a large region between exons 12 and 13 and was derived from four exons (12A-D) of 15, 33, 42, and 3 bp. Exons 12C and 12D together coded for 15 amino acids very similar to the second half of the muscle-specific insert (MSD1) found in N-CAM cDNA from human muscle cell cultures [Dickson, G., Gower, H. J., Barton, C. H., Prentice, H. M., Elsom, V. L., Moore, S. E., Cox, R. D., Quinn, C., Putt, W. & Walsh, F. S. (1987) Cell 50, 1119-1130]; the sequences of 12A and 12B, however, were much less similar to the corresponding region of the MSD1 sequence. Two oligonucleotides, one specific to exons 12A plus 12B and one specific to exon 12C both recognized mRNA species of 6.4 kb, 4.3 kb, and 3.0 kb in chicken cardiac and skeletal muscle and no mRNA species in smooth muscle or brain. The 3' end of clone lambda N101B contained a sequence coding for a potential phosphatidylinositol linkage signal as does the smallest form of brain N-CAM. In heart cell membranes only the 130-kDa N-CAM polypeptide was released by phospholipase C, suggesting that this form of N-CAM is encoded by clone lambda N101B. The other heart N-CAM species (150 kDa and 140 kDa) may be transmembrane forms that include the 12A-D (and possibly other) inserts. Tissue-specific forms of N-CAM can thus be formed by alternative use of multiple small exons that may alter the conformation of the extracellular region of the molecule. Differential use or switching of these small exons in conjunction with the differential expression of larger exons specifying regions associated with the cell membrane and cytoplasmic domains may signal key events in embryogenesis and histogenesis.
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PMID:Four exons encode a 93-base-pair insert in three neural cell adhesion molecule mRNAs specific for chicken heart and skeletal muscle. 320 Aug 47

In embryonic chicken brains, the neural cell adhesion molecule N-CAM is expressed mainly as two polypeptides, the large intracellular-domain polypeptide (ld) (Mr = 160,000) and the small intracellular-domain polypeptide (sd) (Mr = 130,000) chains, that differ in their cytoplasmic domains and that arise by alternative splicing of RNA transcribed from a single gene. There is evidence for a minor N-CAM polypeptide of Mr = 120,000 that is similar to the ld and sd chains for most of its amino-terminal sequence, but which lacks a cytoplasmic domain. We report here the isolation and characterization of a cDNA clone, lambda N151, that appears to encode this third N-CAM polypeptide, which we designate the ssd (small surface-domain) polypeptide chain. The cDNA insert of lambda N151 consists of 2437 base pairs (bp). DNA hybridization and sequencing indicate that the first 1721 bp are nearly identical to the corresponding sequences of clone lambda N208, which encodes the ld chain. Following in the same reading frame, lambda N151 encodes 25 amino acids not present in lambda N208. The rest of lambda N151 consists of a 637-bp noncoding region containing an AATACA polyadenylylation sequence and a 55-bp poly(A) tract. Messenger RNAs complementary to lambda N151 appear later in development than those complementary to the ld and sd chains, and their appearance is correlated with the appearance of the ssd polypeptide. Although the polypeptide encoded by lambda N151 lacks a membrane region that would define a cytoplasmic domain, it does contain at its carboxyl end a relatively hydrophobic stretch of amino acids similar to those seen in precursors of membrane proteins that are attached to membranes via the lipid phosphatidylinositol. We show here that the ssd chain of chicken N-CAM can be released from brain vesicles by treatment with phospholipase C, suggesting that it too may have a phosphatidylinositol anchor. These results define two additional modes by which N-CAM expression can be modulated: by RNA splicing at a new site and by differential membrane attachment of the resulting polypeptide through a lipid intermediate.
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PMID:cDNA clones of the neural cell adhesion molecule (N-CAM) lacking a membrane-spanning region consistent with evidence for membrane attachment via a phosphatidylinositol intermediate. 346 41

Qualitative and quantitative changes in neural cell adhesion molecule (N-CAM) protein and mRNA forms were measured during myogenesis in G8-1 and C2 cell lines. Indirect immunofluorescence assay showed that N-CAM was constitutively expressed by myoblasts in culture and that myotubes appeared to be stained more strongly. These changes were quantified using a dot blot assay. N-CAM levels increased almost 4-fold in G8-1 cells and 15-fold in C2 cells during myogenesis. The kinetics of accumulation of N-CAM were not coordinate with other muscle markers such as creatine kinase or acetylcholine receptor levels, since N-CAM accumulated significantly ahead of these markers. Immunoblotting showed that myogenesis was not associated with changes in the extent of sialylation of N-CAM. However, distinct changes in desialo forms were observed after neuraminidase treatment. Myogenesis was accompanied by increases in 125- and 155-kD desialo forms with minor changes in 120- and 145-kD forms. Biosynthetic labeling studies showed that myoblasts specifically expressed a transmembrane isoform of 145 kD that was phosphorylated and was down-regulated in myotubes. Pulse-chase analysis of myotubes showed that the 120-kD isoform and an isoform of 145 kD that co-migrated with, but was distinct from, the 145 kD transmembrane isoform of myoblasts were precursors of the 125- and 155-kD isoforms, respectively, that accumulated in myotubes. The 125- and 155-kD isoforms in myotubes are linked to the cell membrane via phosphatidylinositol linkage and can be released by phospholipase C. Indirect immunofluorescence analysis showed that phosphatidylinositol specific phospholipase C specifically released N-CAM from the myotube membrane generating N-CAM-free myotubes, while myoblasts were unaffected by this treatment. Three N-CAM mRNA species were observed in mouse muscle cell lines. Myoblasts were characterized by their expression of 6.7- and 5.2-kb transcripts while myotubes express 5.2- and 2.9-kb transcripts. Thus, myogenesis is qualitatively associated with a down regulation of the 6.7-kb transcript and an up regulation of the 5.2- and 2.9-kb transcript.
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PMID:Skeletal muscle neural cell adhesion molecule (N-CAM): changes in protein and mRNA species during myogenesis of muscle cell lines. 365 57

The neural cell adhesion molecule (N-CAM) of rodents comprises three distinct proteins of Mr 180,000, 140,000, and 120,000 (designated N-CAM-180, -140, and -120). They are expressed in different proportions by different tissues and cell types. but the individual contribution of each form to cell adhesion is presently unknown. Previous studies have shown that the two N-CAM species of higher relative molecular mass span the membrane whereas N-CAM-120 lacks a transmembrane domain and can be released from the cell surface by phosphatidylinositol-specific phospholipase C. In this report, we provided evidence that N-CAM-120 contained covalently bound phosphatidylinositol and studied N-CAM-120 from its biosynthesis to its membrane insertion and finally to its release from the cell surface. Evidence was presented showing that the lipid tail of N-CAM-120 contained ethanolamine as is the case for other lipid-linked molecules. The phospholipid anchor was attached to the protein during the first minutes after completion of the polypeptide chain. This process took place in the endoplasmic reticulum as judged from endoglycosidase H digestion experiments. Immediately after a 2-min pulse with [35S]methionine, we detected also a short-lived precursor that had not yet acquired the lipid tail. Pulse-chase studies established that N-CAM-120 was transported to the cell surface from which it was slowly released into the extracellular milieu. The molecules recovered in the incubation medium appeared to have lost all of their bound fatty acid but only around half of the ethanolamine. Upon fractionation of brain tissue, approximately 75% of N-CAM-120 was recovered with a membrane fraction and approximately 25% in a membrane-free supernatant. A small proportion (approximately 6%) was found to be resistant to extraction by non-ionic detergent. A major posttranslational modification of N-CAM is polysialylation. Our results showed that also N-CAM-120 was polysialylated in the young postnatal brain and released in this form from cultured cerebellar cells. The presence of N-CAM in a form that can be released from the cell surface and accumulates in the extracellular fluid suggests a novel mechanism by which N-CAM-mediated adhesion may be modulated.
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PMID:Biosynthesis, membrane association, and release of N-CAM-120, a phosphatidylinositol-linked form of the neural cell adhesion molecule. 369 91

The rodent neural cell adhesion molecule (NCAM) consists of three glycoproteins with Mr of 180,000, 140,000 and 120,000. The Mr 120,000 protein (NCAM-120) has been shown to exist in membrane-bound and soluble forms but the nature of its membrane association and release has remained obscure. We show here that phosphatidylinositol-specific phospholipase C (PI-PLC), but not a phospholipase C of different specificity, releases a substantial proportion of NCAM-120 from brain membranes and solubilizes almost quantitatively NCAM-120 present at the surface of C6 astroglial cells. The PI-PLC effect was highly selective since only one other protein species was detectably released from C6 cells. These results suggest that NCAM-120 is held in the membrane by covalently bound phosphatidylinositol or a closely related lipid in a way similar to several other surface proteins from eukaryotic cells. The presence of NCAM in a form which can be released from the cell surface by a highly selective mechanism raises additional possibilities for modulation and control of cell--cell adhesion.
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PMID:Phosphatidylinositol is involved in the membrane attachment of NCAM-120, the smallest component of the neural cell adhesion molecule. 378 Jun 68

To study the membrane anchoring of the 120 kDa component of the neural cell adhesion molecule N-CAM, the smallest form lacking a transmembrane domain, cultured mouse neural cells were treated with phosphatidylinositol-specific phospholipase C from Staphylococcus aureus. When live cultures of astrocytes and neurons are treated with phosphatidylinositol-specific phospholipase C, N-CAM120 is released into the supernatant. Under these conditions N-CAM140 and N-CAM180 are not released. Phospholipase C from Bacillus cereus or Clostridium perfringens does not release N-CAM120. The embryonic form of N-CAM on astrocytes migrating as a broad band between 120 and 180 kDa is also partially released by phosphatidylinositol-specific phospholipase C as a band migrating between 120 and 160 kDa. These observations suggest novel mechanisms in regulation of N-CAM120 expression on the cell surface and in modulation of N-CAM-mediated cell adhesion.
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PMID:Release of the 120 kDa component of the mouse neural cell adhesion molecule N-CAM from cell surfaces by phosphatidylinositol-specific phospholipase C. 382 37

Nyk/Mer is a recently identified receptor tyrosine kinase with neural cell adhesion molecule-like structure (two immunoglobulin G-like domains and two fibronectin III-like domains) in its extracellular region and belongs to the Ufo/Axl family of receptors. The ligand for Nyk/Mer is presently unknown, as are the signal transduction pathways mediated by this receptor. We constructed and expressed a chimeric receptor (Fms-Nyk) composed of the extracellular domain of the human colony-stimulating factor 1 receptor (Fms) and the transmembrane and cytoplasmic domains of human Nyk/Mer in NIH 3T3 fibroblasts in order to investigate the mitogenic signaling and biochemical properties of Nyk/Mer. Colony-stimulating factor 1 stimulation of the Fms-Nyk chimeric receptor in transfected NIH 3T3 fibroblasts leads to a transformed phenotype and generates a proliferative response in the absence of other growth factors. We show that phospholipase C gamma, phosphatidylinositol 3-kinase/p70 S6 kinase, Shc, Grb2, Raf-1, and mitogen-activated protein kinase are downstream components of the Nyk/Mer signal transduction pathways. In addition, Nyk/Mer weakly activates p90rsk, while stress-activated protein kinase, Ras GTPase-activating protein (GAP), and GAP-associated p62 and p190 proteins are not activated or tyrosine phosphorylated by Nyk/Mer. An analysis comparing the Nyk/Mer signal cascade with that of the epidermal growth factor receptor indicates substrate preferences by these two receptors. Our results provide a detailed description of the Nyk/Mer signaling pathways. Given the structural similarity between the Ufo/Axl family receptors, some of the information may also be applied to other members of this receptor tyrosine kinase family.
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PMID:Mitogenic signals and transforming potential of Nyk, a newly identified neural cell adhesion molecule-related receptor tyrosine kinase. 852 23


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