Small GTPases and tyrosine kinases coregulate a molecular switch in the phosphoinositide 3-kinase regulatory subunit.
Cancer Cell
; 1(2): 181-91, 2002 Mar.
Article
em En
| MEDLINE
| ID: mdl-12086876
ABSTRACT
Phosphoinositide 3-kinase (PI3K) type IA is a heterodimer of a catalytic subunit, p110, and a regulatory subunit, p85. Here we show that p85 contains a GTPase-responsive domain and an inhibitory domain, which together form a molecular switch that regulates PI3K. H-Ras and Rac1 activate PI3K by targeting the GTPase-responsive domain. The stimulatory effect of these molecules, however, is blocked by the inhibitory domain, which functions by binding to tyrosine-phosphorylated molecules and is neutralized by tyrosine phosphorylation. The complementary effects of tyrosine kinases and small GTPases on the p85 molecular switch result in synergy between these two classes of molecules toward the activation of the PI3K/Akt pathway.
Buscar no Google
Base de dados:
MEDLINE
Assunto principal:
Proteínas Tirosina Quinases
/
Proteínas Proto-Oncogênicas
/
Proteínas Serina-Treonina Quinases
/
Fosfatidilinositol 3-Quinases
/
GTP Fosfo-Hidrolases
Limite:
Animals
Idioma:
En
Ano de publicação:
2002
Tipo de documento:
Article