Heterodimeric phosphoinositide 3-kinase consisting of p85 and p110 beta is synergistically activated by the beta gamma subunits of G proteins and phosphotyrosyl peptide
Heterodimeric phosphoinositide 3-kinase consisting of p85 and p110 beta is synergistically activated by the beta gamma subunits of G proteins and phosphotyrosyl peptide
复制标题
DOI：
10.1074/jbc.272.39.24252
复制
发表时间：
1997-09-26
影响因子：
4.8
通讯作者：
Katada, T
中科院分区：
文献类型：
--
作者：
Kurosu, H;Maehama, T;Katada, T
磷脂酰肌醇3-激酶（Phosphoinositide 3-kinase，PI 3-kinase）是参与多种受体刺激的细胞反应的关键信号酶。具有内在或相关酪氨酸激酶活性的受体募集由110-kDa催化亚基（p110）和85-kDa调节亚基（p85）组成的异二聚体PI 3-kinase。我们分离到一种能被G蛋白β-γ亚基激活的PI 3-激酶G β γ敏感的PI 3-激酶似乎是由p110 β和p85 β组成的异源二聚体抑制性GTP结合蛋白的GDP结合α亚基抑制G β γ的刺激，通过同时加入根据胰岛素受体底物-1的氨基酸序列合成的磷酸酪氨酰肽，G β γ的刺激作用显著增强。用COS-7细胞中表达的重组p110 β/p85 α及其cDNA可以观察到这种酶性质。相反，在同一大鼠肝脏中，另一种由p110 α和p85组成的异源二聚体PI 3-激酶，以及重组的p110 α/p85 α，不被G β γ激活，尽管它们的活性被磷酸酪氨酰肽激活。这些结果表明，阿拉伯茶p110 β/p85 PI 3-激酶可能是由两种不同类型的膜受体，一个具有酪氨酸激酶活性和其他激活GTP结合蛋白的合作方式进行调节。
Phosphoinositide 3-kinase (PI 3-kinase) is a key signaling enzyme implicated in variety of receptor-stimulated cell responses, Receptors with intrinsic or associated tyrosine kinase activity recruit heterodimeric PI 3-kinases consisting of a 110-kDa catalytic subunit (p110) and an 85-kDa regulatory subunit (p85). We separated a PI 3-kinase that could be stimulated by the beta gamma subunits of G protein (G beta gamma) from rack liver, The G beta gamma-sensitive PI 3-kinase appeared to be a heterodimer consisting of p110 beta and p85 (or their related subunits), The stimulation by G beta gamma was inhibited by the GDP-bound alpha subunit of the inhibitory GTP-binding protein, Moreover, the stimulatory action of G beta gamma was markedly enhanced by the simultaneous addition of a phosphotyrosyl peptide synthesized according to the amino acid sequence of the insulin receptor substrate-1, Such enzymic properties could be observed with a recombinant p110 beta/p85 alpha expressed in COS-7 cells with their cDNAs, In contrast, another heterodimeric PI 3-kinase consisting of p110 alpha and p85 in the same rat liver, together with a recombinant p110 alpha/p85 alpha, was mot activated by G beta gamma, although their activities were stimulated by the phosphotyrosyl peptide. These results indicate khat p110 beta/p85 PI 3-kinase may be regulated in a cooperative manner by two different types of membrane receptors, one possessing tyrosine kinase activity and the other activating GTP-binding proteins.