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Titolo:
MUTATIONAL ACTIVATION OF PP60(C-SRC) LEADS TO A TUMORIGENIC PHENOTYPEIN A PRENEOPLASTIC SYRIAN-HAMSTER EMBRYO CELL-LINE
Autore:
LANSING TJ; TURK BF; KANNER SB; GILMER TM;
Indirizzi:
GLAXO WELLCOME RES & DEV LTD,DEPT CANC BIOL,RCII,ROOM 806 RES TRIANGLE PK NC 27709 GLAXO WELLCOME RES & DEV LTD,DEPT CANC BIOL RES TRIANGLE PK NC 27709 BRISTOL MYERS SQUIBB PHARMACEUT RES INST SEATTLE WA 98121
Titolo Testata:
Cancer research
fascicolo: 10, volume: 57, anno: 1997,
pagine: 1962 - 1969
SICI:
0008-5472(1997)57:10<1962:MAOPLT>2.0.ZU;2-W
Fonte:
ISI
Lingua:
ENG
Soggetto:
SODIUM DODECYL-SULFATE; SRC GENE; TYROSINE PHOSPHORYLATION; MONOCLONAL-ANTIBODIES; V-SRC; C-SRC; GEL-ELECTROPHORESIS; REGULATORY DOMAIN; CARBOXY TERMINUS; PP60C-SRC;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Science Citation Index Expanded
Citazioni:
47
Recensione:
Indirizzi per estratti:
Citazione:
T.J. Lansing et al., "MUTATIONAL ACTIVATION OF PP60(C-SRC) LEADS TO A TUMORIGENIC PHENOTYPEIN A PRENEOPLASTIC SYRIAN-HAMSTER EMBRYO CELL-LINE", Cancer research, 57(10), 1997, pp. 1962-1969

Abstract

Previous studies indicated that overexpression of wild-type avian c-src cannot induce neoplastic transformation of NIH 3T3 cells, In this study, we isolated and characterized novel spontaneously derived transforming mutants of avian pp60(c-src) from a Syrian hamster embryo-derived cell line, 10W, transfected with the avian c-src gene, Seventeen independently derived transfected 10W cell clones were injected into athymic nude mice. After a latency period, tumors eventually arose and were established in culture, The tumorigenic phenotype was always accompanied by the presence of the avian c-src DNA and functional expressionof pp60(c-src) However, most of the tumor-derived cell lines expressed an electrophoretically altered form of pp60(c-src), suggesting mutations in src. Consistent with this hypothesis, DNAs isolated from the tumor-derived lines, but not the parental 10W cell lines, morphologically transformed NIH 3T3 cells in a focus-forming assay, We characterized pp60(c-src) in detail from three of the tumor-derived lines: 4AT, JET, and E2T, Two of these lines contained mutations within the exogenous c-src coding region. Line 4AT has an internal repeat of 29 amino acids immediately following Gln-513, which disrupts the spacing between the end of the kinase domain and Tyr-527, the negative regulatory site in pp60(c-src). Line 4BT has a 5-bp deletion following Phe-520, which results in loss of Tyr-527, However, the DNA sequence of the coding region of pp60(c-src) from a third line, E2T, was completely wild type, Cyanogen bromide cleavage analyses of the altered pp60(c-src) from lines 4AT and 4BT showed that Tyr-527, the site of negative regulation ofc-src, is not phosphorylated, but Tyr-416, the site of in vitro autophosphorylation, is phosphorylated. However, in line E2T, Tyr-527 was phosphorylated, and Tyr-416 was phosphorylated to a lesser extent. Additionally, two proteins that indicate activation of src, p85 cortactin and p120(cas), are phosphorylated in at least six of the tumor-derivedcell lines, although to a lesser extent in line E2T, These results suggest that dephosphorylation of Tyr-527 and phosphorylation of Tyr-416correlate with activation of pp60(c-src) in the tumor-derived lines 4AT and 4BT, respectively, However, in line E2T, the high levels of pp60(c-src), in combination with a partial activation of the pp60(c-src) protein as indicated by phosphorylation of Tyr-416, appear to be involved in the neoplastic process, rather than mutation.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 05/07/20 alle ore 00:56:20