Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

---

Query: EC:2.7.10.2 (focal adhesion kinase)
44,029 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Mouse P19 embryonal carcinoma (EC) cells express on their surfaces a Thy-1 glycoprotein. The expression of Thy-1 at the mRNA and protein levels is down-regulated during differentiation induced by retinoic acid (RA). Thy-1 is also expressed in human NTERA-2 EC cells, but its expression is not down-regulated during RA-induced differentiation. As a first step towards understanding differential regulation of the mouse and human Thy-1 gene in EC cells, we have introduced genomic DNA fragments encompassing the mouse or human Thy-1 gene into NTERA-2 and P19-derived cells and analyzed surface properties of the transfectants. In the transient transfection assay, both mouse and human Thy-1 genes were expressed on cell surfaces at comparable levels. P19-derived stable transfectants exhibited great clonal variations in the expressions of the transfected Thy-1 gene products, which in part reflected copy numbers. There was no simple correlation between the expression of the transfected Thy-1 gene and two stem cell surface markers, TEC-1 and TEC-4. In the course of differentiation induced by RA several clones with a surface phenotype of EC cells exhibited a significant decrease in the expression of the transfected mouse Thy-1, whereas expression of the human Thy-1 was less efficiently down-regulated. The results suggest the presence of multiple cis- and trans-acting elements controlling expression of the mouse and human Thy-1 genes in P19 EC cells and their differentiated derivatives.
...
PMID:Differential expression of the mouse and human Thy-1 gene in embryonal carcinoma cells. 136 23

Embryonal carcinoma cells defective in their ability to adhere to tissue culture dishes were isolated from mutagenized P19X1 and P19S1801A1 cells. Three independently isolated variants were analyzed for their morphology, surface properties and ability to differentiate in vitro. Two of the mutant cell lines expressed similar amounts of stage-specific embryonic antigens TEC-1, TEC-4 and Thy-1 as parental cells, whereas all three showed significant reduction in the expression of uvomorulin as determined by a direct radioantibody binding assay. Variant cells exhibited a decrease in their ability to aggregate in media with or without CA2+ and were unable to form compact aggregates when cultured for two days in complete culture media. In the presence of retinoic acid variant cells formed aggregates which exhibited significantly lower frequency neuron formation after transfer to tissue culture dishes. The combined data indicate that the adhesion-defective phenotype of P19-derived cells is in part the result of a reduced surface expression of uvomorulin.
...
PMID:Changes in surface glycoconjugates in adhesion-defective variants of P19 embryonal carcinoma cells. 166 95

Embryonal carcinoma cells defective in the expression of developmentally regulated carbohydrate epitope of teratocarcinoma cells (TEC-1) were isolated from mutagenized P19X1 and P19S1801A1 cells by a single-step selection technique using monoclonal antibody TEC-01 conjugated to plant toxin ricin. Three independently isolated mutant cell lines were characterized in detail. Analysis of the expression of the TEC-1 epitope in somatic cell hybrids constructed between wild-type and mutant cells and between two mutant cell types revealed that the mutant phenotypes are recessive and that the mutants belong to, at least, two complementation groups. Each mutant cell line exhibited a unique binding pattern of four monoclonal antibodies and five lectins, and different properties of large glycopeptides were distinguished by Sephadex G-50 column chromatography. The combined data suggest that our mutants identify three genes involved in the synthesis of embryoglycan, one of which appears to be the regulatory or structural gene for fucosyltransferase. One mutant cell line was completely deprived of embryoglycan and several carbohydrate structures typical of early embryonic and embryonal carcinoma cells; however, the cells were similar to parental cells in their morphology, their ability to form aggregates when cultured in suspension, their ability to differentiate into neuron-like cells after treatment with retinoic acid, and their ability to form tumors composed of embryonal carcinoma cells. Thus, embryoglycan is not required for the expression of a number of properties of the embryonal carcinoma phenotype.
...
PMID:Mutants of embryonal carcinoma cells defective in the expression of embryoglycan. 244 94

The expression and properties of mouse embryonic antigens, recognized by monoclonal antibody TEC-02, were analyzed in teratocarcinoma-derived cell lines. TEC-2 antigens were found in the majority of the parietal endoderm cells PYS-2 and in a fraction of cultured embryonal carcinoma cells but not in other cell lines tested. During the course of retinoic acid-induced differentiation of embryonal carcinoma cells F9, the expression of TEC-2 was transiently increased. Immunolabeling of extracts from F9 and PYS-2 cells separated by sodium dodecyl sulfate-polyacrylamide gel electrophoresis revealed that TEC-2 antigens are polydisperse glycoconjugates of high molecular weight (mostly greater than 100,000). The TEC-2 epitope was shown to be carbohydrate which in F9 cells might be attached to the same carrier as another developmentally regulated carbohydrate epitope TEC-1. The TEC-2 antigens, isolated by indirect immunoprecipitation, were degraded by extensive pronase digestion or mild alkaline treatment to mostly large products. Immunostaining of glycolipid standards suggested that TEC-2 epitope involves the GalNAc beta 1----4Gal beta 1----4R sequence. Combined data indicate that TEC-2 is a new developmentally regulated carbohydrate epitope carried in embryonal carcinoma cells predominantly on glycoprotein-bound large carbohydrates.
...
PMID:The epitope of mouse embryonic antigen(s) recognized by monoclonal antibody TEC-02 is a carbohydrate carried by high-molecular-weight glycoconjugates. 244 54

Embryonal carcinoma cells carry on their surfaces carbohydrate antigens that are also expressed in early embryonic cells. We report here the expression and properties of a new developmentally regulated carbohydrate epitope, which is defined by a monoclonal antibody TEC-05. This antibody was generated by immunization of a rat with mouse embryonal carcinoma cells P19S1801A1. By immunofluorescence, the TEC-5 epitope was first detected on 8-cell-stage mouse embryos and was present on all subsequent stages of preimplantation development. Absorption analysis revealed that TEC-5 epitope was expressed only on a limited number of adult mouse tissues. In the direct radioantibody binding assay, TEC-05 reacted strongly with OTF9-63 cells and with some of the mouse embryonal carcinoma cell lines tested. Its reaction with differentiated cell lines was weak or undetectable. In the course of differentiation of OTF9-63 cells induced by retinoic acid, the epitope disappeared with the onset of morphological differentiation. The binding of the antibody to OTF9-63 cells was inhibited to 50% by 10-50 microM N-acetyllactosamine and lactose. Immunolabelling of extracts from OTF9-63 cells separated by sodium-dodecyl-sulfate (SDS) polyacrylamide gel electrophoresis revealed that TEC-5 epitope was carried by high-molecular-weight glycoconjugates (molecular weight greater than 100,000). Molecules, isolated from [3H]-fucose-labelled OTF9-63 cells by indirect immunoprecipitation with TEC-05 antibody, were degraded by extensive pronase digestion or mild alkaline treatment to large carbohydrate chains that were excluded from a Sephadex G-50 column. Direct evidence that TEC-05 antibody bound to embryoglycan was obtained using a modified Farr's assay. The antibody was found to inhibit adhesion of F9 and OTF9-63 cells to substratum. The inhibitory effect, which could be abrogated by lactose, seemed to be specific, because another IgM monoclonal antibody which also binds to embryoglycan had no effect. Combined data indicated that TEC-05 antibody recognizes a carbohydrate epitope which is involved in cell-substratum adhesion of F9 cells and which provides a new marker for structure-function studies of stage-specific embryonic antigens.
...
PMID:Inhibition of adhesion of F9 embryonal carcinoma cells to substratum by a novel monoclonal antibody, TEC-05, reactive with a developmentally regulated carbohydrate epitope. 245 92

Most developmentally regulated epitopes identified on embryonal carcinoma cells and murine preimplantation embryos are associated with a glycoprotein-bound large glycan called embryoglycan. To prepare monoclonal antibodies recognizing other, less immunogenic stage-specific embryonic epitopes, we used embryoglycan-negative embryonal carcinoma cells P19XT.1.1 as immunogen. One monoclonal antibody prepared by this strategy was found to react specifically with mouse embryonal carcinoma and embryo-derived stem cell lines. The target epitope, TEC-4, was found to be expressed on eggs and two-cell embryos but was undetectable on later stages of mouse embryos and adult mouse tissues. NaDodSO4/PAGE of immunoaffinity-isolated antigen revealed that TEC-4 epitope is associated with glycoproteins of apparent Mr 120,000 and 240,000. The epitope was resistant to oxidation by sodium periodate and to digestion by endoglycosidase F but was sensitive to treatment with protein-denaturing agents and proteases, which suggested that the epitope is located in the protein moiety of the molecule. In the course of retinoic acid-induced differentiation of embryonal carcinoma cells the epitope disappeared before the onset of morphological differentiation. The combined data indicate that TEC-4 is an unusual stage-specific embryonic antigen that may be amenable to direct genetic analysis.
...
PMID:Unusual stage-specific embryonic antigen (TEC-4) defined by a monoclonal antibody to embryonal carcinoma cells defective in the expression of embryoglycan. 257 58

We report an unusual hyperdiploid karyotype characterized by the simultaneous occurrence of tetrasomy 21 and trisomy 8 detected during early blastic evolution of a BCR-ABL-negative chronic myeloproliferative disorder. Blast cells from this patient showed a striking response to all-trans-retinoic acid (ATRA)-induced differentiation as evaluated by CD15 expression following in vitro exposure to this inducer. Our report represents the first description of such a composite karyotype in human hematologic malignancies.
...
PMID:Simultaneous occurrence of tetrasomy 21 and trisomy 8 in a patient with early blastic metamorphosis of chronic myeloproliferative disorder. 766 24

Focal adhesion kinase, FAK, is a unique protein tyrosine kinase found in cellular focal adhesions. It is widely expressed and highly phosphorylated during embryogenesis. To examine the function of FAK in cell differentiation, we made FAK-deficient embryonic stem (ES) cells by homologous recombination. However, FAK-deficiency did not interfere with differentiation of the ES cells into cells of three germ layers when implanted subcutaneously into nude mice or when treated with retinoic acid in vitro, nor was there any evidence of defects in hematopoiesis in vitro.
...
PMID:Focal adhesion kinase is not essential for in vitro and in vivo differentiation of ES cells. 772 50

It has recently been demonstrated that mutations in the gene for Bruton's tyrosine kinase (BTK) are responsible for X-linked agammaglobulinemia. Southern blot analysis and sequencing of cDNA were used to document deletions, insertions, and single base pair substitutions. To facilitate analysis of BTK regulation and to permit the development of assays that could be used to screen genomic DNA for mutations in BTK, we determined the genomic organization of this gene. Subcloning of a cosmid and a yeast artificial chromosome showed that BTK is divided into 19 exons spanning 37 kilobases of genomic DNA. Analysis of the region 5' to the first untranslated exon revealed no consensus TATAA or CAAT boxes; however, three retinoic acid binding sites were identified in this region. Comparison of the structure of BTK with that of other nonreceptor tyrosine kinases, including SRC, FES, and CSK, demonstrated a lack of conservation of exon borders. Information obtained in this study will contribute to our understanding of the evolution of nonreceptor tyrosine kinases. It will also be useful in diagnostic studies, including carrier detection, and in studies directed towards gene therapy or gene replacement.
...
PMID:The genomic structure of human BTK, the defective gene in X-linked agammaglobulinemia. 792 35

The establishment and the biological properties of a new leukemic cell line (KBM-5) derived from a patient in the blastic phase of chronic myelogenous leukemia are described. The cells exhibited multiple copies of the Philadelphia chromosome, and a high level of p210Bcr-Abl kinase activity was detected with rabbit anti-Abl and anti-Bcr (exon 3) peptide antisera. Use of specific primers and polymerase chain reaction followed by Southern blotting revealed that KBM-5 cells carried a bcr3-ABLII splice junction. While a normal BCR message was detected, no normal ABL message was found. The cells were phenotypically myeloid with monocytic differentiation. The high cloning efficiency in semisolid media was independent of the presence of exogenous colony-stimulating factors. In vitro exposure to induces of differentiation, such as retinoic acid, dimethyl sulfoxide, or hemin, failed to influence the growth rate of the cells and their level of differentiation. KBM-5 cells are highly resistant to the antiproliferative action of recombinant alpha- and gamma-interferons. Although sensitive to recombinant tumor necrosis factor alpha, they were completely resistant to natural killer cell action. KBM-5 cells constitutively expressed mRNA for tumor necrosis factor alpha but not for gamma-interferon, other interleukins, or hematopoietic growth factors. The KBM-5 cells that were transplanted into SCID mice manifested metastatic potential and tissue invasiveness similar to the way leukemic cells in humans do. This new KBM-5 cell line represents a helpful model for examining in vitro and in vivo modulation of the growth and properties of leukemic cells by using biological and chemotherapeutic agents.
...
PMID:Biological properties and growth in SCID mice of a new myelogenous leukemia cell line (KBM-5) derived from chronic myelogenous leukemia cells in the blastic phase. 833 66


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

---