SYNERGISTIC REGULATION OF PHOSPHOINOSITIDE 3-KINASE

点击翻译按钮获取中文摘要

The following results were obtained by establishing the Chinese hamster ovary cells stably expressing GTP-binding protein-coupled receptors, adenosine A1 receptors or fMLP receptors: (1) Adenosine orfMLP activated Akt in the cells (2) This activation was-synergistically increased by insulin (3) The effect of adenosine was abolished by treatment of the cells with pertussis toxin or transfection with beta ARK-CT peptide (4) expression of the p85 regulatory subunit of PI 3-kinase inhibited the action of adenosine (5) expression of p110beta increased markedly the action of adenosine (6) Kinase-dead p110beta prevented the action of adenosine (7) Kinase-dead p110alpha showed little effect (8) An inhibitor of tyrosine kinases inhibited the action of adenosine but a Src family-specific inhibitor PP2 had no effect (9) PP2 prevented the adenosine-induced Erk activation. These results indicated that GPCR activates Akt by a Gbetagama and p110beta-dependent pathway. Tyrosine kinase other than Src family members is also necessary for this activation.