A novel 55-kDa regulatory subunit for phosphatidylinositol 3-kinase structurally similar to p55PIK is generated by alternative splicing of the p85 alpha gene
A novel 55-kDa regulatory subunit for phosphatidylinositol 3-kinase structurally similar to p55PIK is generated by alternative splicing of the p85 alpha gene
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DOI：
10.1074/jbc.271.10.5317
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发表时间：
1996-03-08
影响因子：
4.8
通讯作者：
Asano, T
中科院分区：
文献类型：
--
作者：
Inukai, K;Anai, M;Asano, T
磷脂酰肌醇3-激酶由一个110-kDa的催化亚基和一个调节亚基组成，在多种细胞信号转导机制中发挥重要作用。我们用P-32标记的人IRS-1蛋白筛选了大鼠脑cDNA表达文库，并克隆了很可能由p85 α基因产物选择性剪接产生的cDNA。这些cDNA被证明编码一个55 kDa的蛋白质（p55 α），含有两个SH 2结构域和一个p85 α的SH 2间结构域，但既没有bcr结构域，也没有SH 3同源结构域。有趣的是，p55 α在其NH 2末端含有独特的34个氨基酸序列，其不包括在p85 α氨基酸序列中。该34个氨基酸的部分被揭示为与p55 PIK（p55 γ）在长度上相当，两者之间具有高度同源性，这表明p55 α和p55 γ的这些NH 2末端结构域可能具有p85不具有的特定作用。p55 α mRNA的表达在脑中最丰富，但在大多数大鼠组织中普遍存在。此外，应该注意到，通过用编码p85 α SH 3结构域的cDNA探针进行北方印迹，肌肉中p85 α mRNA的表达几乎低到检测不到，而p55 α的表达可以容易地检测到。这些结果表明，p55 α可能发挥独特的调节作用的磷脂酰肌醇3-激酶在大脑和肌肉。
Phosphatidylinositol 3-kinase, which is composed of a 110-kDa catalytic subunit and a regulatory subunit, plays important roles in various cellular signaling mechanisms. We screened a rat brain cDNA expression library with P-32-labeled human IRS-1 protein and cloned cDNAs that were very likely to be generated by alternative splicing of p85 alpha gene products. These cDNAs were demonstrated to encode a 55-kDa protein (p55 alpha) containing two SH2 domains and an inter-SH2 domain of p85 alpha but neither a bcr domain nor a SH3 homology domain. Interestingly, p55 alpha contains a unique 34-amino acid sequence at its NH2 terminus, which is not included in the p85 alpha amino acid sequence. This 34-amino acid portion was revealed to be comparable with p55PIK (p55 gamma) in length, with a high homology between the two, suggesting that these NH2-terminal domains of p55 alpha and p55 gamma may have a specific role that p85 does not. The expression of p55 alpha mRNA is most abundant in the brain, but expression is ubiquitous in most rat tissues. Furthermore, it should be noted that the expression of p85 alpha mRNA in muscle is almost undetectably low by Northern blotting with a cDNA probe coding for the p85 alpha SH3 domain, while the expression of p55 alpha can be readily detected. These results suggest that p55 alpha may play an unique regulatory role for phosphatidylinositol 3-kinase in brain and muscle.