Role of phosphatidylinositol-3-kinase in insulin receptor signaling: studies with inhibitor, LY294002.
Role of phosphatidylinositol-3-kinase in insulin receptor signaling: studies with inhibitor, LY294002.
复制标题
DOI：
10.1006/bbrc.1994.2480
复制
发表时间：
1994-10
影响因子：
3.1
通讯作者：
V. Sánchez-Margalet;I. Goldfine;C. Vlahos;C. Sung
中科院分区：
文献类型：
--
作者：
V. Sánchez-Margalet;I. Goldfine;C. Vlahos;C. Sung
为了研究磷脂酰肌醇-3-激酶(PI3K)在胰岛素作用中的作用，我们使用了PI3K的特异性抑制剂LY294002，并在高表达人胰岛素受体的小鼠3T3成纤维细胞中检测了胰岛素的五项生物学功能。LY294002对胰岛素受体β亚基和胰岛素受体底物1(IRS-1)的酪氨酸磷酸化均无影响，也不影响PI3K的P85亚基与IRS-1的结合。但LY294002部分抑制胰岛素刺激的葡萄糖摄取、氨基酸摄取和蛋白质合成，而完全抑制胰岛素刺激DNA合成和p70S6激酶的激活。这些数据表明：1)PI3K在胰岛素的各种功能中起着关键作用；2)胰岛素受体存在多种信号通路(PI3K依赖和PI3K非依赖)。
In order to study the role of phosphatidylinositol-3-kinase (PI3K) in insulin action, we employed a specific inhibitor of PI3K, LY294002, and measured five biological functions of insulin in mouse 3T3 fibroblasts overexpressing human insulin receptors. LY294002 had no effect on tyrosine phosphorylation of both the insulin receptor beta-subunit and insulin receptor substrate 1 (IRS-1) and did not influence the association of the p85 subunit of PI3K with IRS-1. However, LY294002 partially inhibited insulin stimulated glucose uptake, amino acid uptake and protein synthesis, while it completely inhibited insulin stimulation of DNA synthesis and p70 S6 kinase activation. These data suggest that: 1) PI3K plays a crucial role in various functions of insulin; and 2) there exist multiple signaling pathways (both PI3K dependent and PI3K independent) for the insulin receptor.