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Titolo:
GROWTH-INHIBITION BY DOMINANT-NEGATIVE MUTATIONS OF THE NEU-ENCODED ONCOPROTEIN
Autore:
SCHLEGEL J; TRENKLE T; STUMM G; KIESSLING M;
Indirizzi:
UNIV MARBURG,MED CTR,DEPT NEUROPATHOL,BALDINGERSTR D-35043 MARBURG GERMANY UNIV HEIDELBERG,INST NEUROPATHOL HEIDELBERG GERMANY
Titolo Testata:
International journal of cancer
fascicolo: 1, volume: 70, anno: 1997,
pagine: 78 - 83
SICI:
0020-7136(1997)70:1<78:GBDMOT>2.0.ZU;2-Z
Fonte:
ISI
Lingua:
ENG
Soggetto:
SCHWANN-CELL LINEAGE; NERVOUS-SYSTEM; RECEPTOR OLIGOMERIZATION; MONOCLONAL-ANTIBODIES; NEUREGULIN RECEPTOR; SIGNAL-TRANSDUCTION; CARDIAC DEVELOPMENT; POINT MUTATION; ERBB-2 GENE; ONCOGENE;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Science Citation Index Expanded
Citazioni:
29
Recensione:
Indirizzi per estratti:
Citazione:
J. Schlegel et al., "GROWTH-INHIBITION BY DOMINANT-NEGATIVE MUTATIONS OF THE NEU-ENCODED ONCOPROTEIN", International journal of cancer, 70(1), 1997, pp. 78-83

Abstract

In the present study, kinase-deficient mutants of the neo gene were constructed in order to generate dominant-negative receptor molecules, which should abolish phosphorylation of receptor complexes, One construct carried a mutation of the putative ATE-binding site (K758M), whilethe other mutant was generated by deletion of the kinase domain (ID400), Neither receptor showed phosphorylation by in vitro kinase assay. When NIH3T3 fibroblasts were co transfected by the oncogenic neu gene and one of either construct, the transforming effect could be partially reversed, Therefore, kinase-negative mutations of the neo-encoded receptor seemed to have a dominant-negative effect on the action of the activated protein, To test this hypothesis, rat neurinoma cell lines containing oncogenic neu genes were transfected with the constructs. Expression of the kinase-defective mutants and reduced phosphorylation could be detected in different clones derived from single transfected cells, Striking growth inhibition and reduction of colony formation in soft agar were observed in these cell lines when compared with untransfected cells, Thus, kinase-deficient mutants exert a dominant-negativeeffect on phosphorylation of receptor complexes, resulting in a reversion of the transformed phenotype. (C) 1997 Wiley-Liss, Inc.

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Documento generato il 16/07/20 alle ore 06:40:56