Direct association of p110 beta phosphatidylinositol 3-kinase with p85 is mediated by an N-terminal fragment of p110 beta.

AUTOR(ES)

Hu, P

RESUMO

Phosphatidylinositol (PI) 3-kinase is a heterodimeric enzyme of 85-kDa (p85) and 110-kDa (p110) subunits implicated in mitogenic signal transduction by virtue of its activation in cells transformed by diverse viral oncoproteins and treated with various growth factors. We have identified a domain in p110 that mediates association with p85 in vitro and in intact cells. A glutathione S-transferase fusion protein containing the N-terminal 171 amino-acids of p110 beta bound to free p85 in cell lysates. This fusion protein also bound directly to p85 immobilized on nitrocellulose filters. An epitope-tagged fragment containing amino acids 31 to 150 of p110 beta associated with p85 upon expression in intact cells. Expression of either an N-terminal fragment of p110 beta or the p85 inter-SH2 domain, which mediates association with p110, reduced the association of endogenous PI 3-kinase activity with the activated platelet-derived growth factor receptor in intact cells. Hence, these defined regions of p85 and p110 mediate the interaction between the two subunits of PI 3-kinase.

Documentos Relacionados

• Phosphatidylinositol 3-kinase activation is mediated by high-affinity interactions between distinct domains within the p110 and p85 subunits.
• Interaction of the p85 subunit of PI 3-kinase and its N-terminal SH2 domain with a PDGF receptor phosphorylation site: structural features and analysis of conformational changes.
• Phosphatidylinositol 3-kinase mediates epidermal growth factor-induced activation of the c-Jun N-terminal kinase signaling pathway.
• Regulation of the p85/p110 Phosphatidylinositol 3′-Kinase: Stabilization and Inhibition of the p110α Catalytic Subunit by the p85 Regulatory Subunit
• Tyrosine 1101 of Tie2 Is the Major Site of Association of p85 and Is Required for Activation of Phosphatidylinositol 3-Kinase and Akt