Tyrosine phosphorylation of NOS3 in a breast cancer cell line and Src-transformed cells.
Oncol Rep
; 11(5): 1059-62, 2004 May.
Article
em En
| MEDLINE
| ID: mdl-15069547
ABSTRACT
We investigated the tyrosine phosphorylation of NOS3 by active Src. In a cell line derived from human breast cancer, BT474, we found activation of c-Src and tyrosine phosphorylation of NOS3. Phosphorylation of NOS3 was suppressed by treatment of BT474 with PP1, an Src kinase inhibitor, in a dose-dependent manner, suggesting that phosphorylation of NOS3 is catalyzed by active c-Src. Phosphorylation of NOS3 was further examined by a series of Src mutants. In cells expressing v-Src, substantial phosphorylation of NOS3 was observed, whereas NOS3 phosphorylation was not evident in cells expressing c-Src. Similarly, NOS1 was also phosphorylated in cells expressing v-Src. Consistently, in cells expressing a temperature-sensitive mutant of v-Src, NOS3 phosphorylation was temperature-dependent. Moreover, transforming mutant of c-Src, Y527Fc-Src, could activate NOS3 phosphorylation. In contrast, non-myristoylated form of v-Src, G2Av-Src and a kinase-inactive mutant of v-Src, K295Mv-Src, could not activate NOS3 phosphorylation. Taken together, our results suggest that active, membrane-bound form of Src can induce constitutive phosphorylation of NOS3.
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Base de dados:
MEDLINE
Assunto principal:
Neoplasias da Mama
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Proteínas Proto-Oncogênicas pp60(c-src)
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Fosfotirosina
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Óxido Nítrico Sintase
Limite:
Animals
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Female
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Humans
Idioma:
En
Ano de publicação:
2004
Tipo de documento:
Article