Phosphatidylinositol-3-kinase activity is required for the anti-ig-mediated growth inhibition of a human B-lymphoma cell line.
Blood
; 87(1): 202-10, 1996 Jan 01.
Article
em En
| MEDLINE
| ID: mdl-8547643
ABSTRACT
Stimulation of B lymphocytes through the Ig receptor initiates a cascade of biochemical changes, which can ultimately lead to either activation and growth, or cell-cycle arrest and cell death. One of the critical events that occurs in both cases is the activation of tyrosine kinases, and the resulting phosphorylation of a variety of proteins on tyrosine residues. In this report we identify one of the substrates of phosphorylation as the 85-kD subunit of the enzyme phosphatidylinositol-3 kinase (PI3K), and show that both anti-IgM and anti-IgD stimulation results in an increase in the anti-phosphotyrosine-precipitable PI3K activity. Furthermore, we show that the potent and specific inhibitor of PI3K, Wortmannin, can completely abrogate anti-Ig-mediated growth inhibition without affecting tyrosine kinase induction or protein kinase C (PKC) activation. Treatment of intact cells with Wortmannin results in an irreversible decrease in anti-Ig-induced PI3K activity, suggesting that the effect of Wortmannin on anti-Ig-mediated growth inhibition is caused by its inactivation of PI3K activity. Taken together, these data show that activation of PI3K is a critical component of the anti-Ig-initiated signaling cascade that leads to growth inhibition of human B lymphoma cells.
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Base de dados:
MEDLINE
Assunto principal:
Imunoglobulina D
/
Imunoglobulina M
/
Linfócitos B
/
Receptores de Antígenos de Linfócitos B
/
Transdução de Sinais
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Processamento de Proteína Pós-Traducional
/
Linfoma Difuso de Grandes Células B
/
Fosfotransferases (Aceptor do Grupo Álcool)
Limite:
Humans
Idioma:
En
Ano de publicação:
1996
Tipo de documento:
Article