Inositol 1,4,5,6-tetrakisphosphate is phosphorylated in rat liver by a 3-kinase that is distinct from inositol 1,4,5-trisphosphate 3-kinase.
Inositol 1,4,5,6-tetrakisphosphate is phosphorylated in rat liver by a 3-kinase that is distinct from inositol 1,4,5-trisphosphate 3-kinase.
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肌醇 1,4,5,6-四磷酸在大鼠肝脏中被不同于肌醇 1,4,5-三磷酸 3-激酶的 3-激酶磷酸化。
DOI：
10.1016/s0021-9258(17)41784-4
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发表时间：
1994
期刊：
影响因子：
--
通讯作者：
S. Shears
中科院分区：
文献类型：
--
作者：
A. Craxton;C. Erneux;S. Shears
肝匀浆将磷酸化肌醇1，4，5，6-四磷酸专门转化为肌醇1，3，4，5，6-五磷酸。大约30%的磷酸化活性与细胞的颗粒部分相关，与之相反的是肌醇3，4，5，6-四磷酸1-激酶，其是90%可溶的。通过阴离子交换层析将可溶性1-激酶活性与磷酸化肌醇1，4，5，6-四磷酸的可溶性活性分离。还发现这两种磷酸化活性被肌醇1，3，4-三磷酸不同程度地抑制（3-激酶的IC 50> 100 μ M; 1-激酶的IC 50 < 1 μ M）。因此，我们已经证明，肌醇1，4，5，6-四磷酸直接被β-激酶磷酸化，并且肌醇3，4，5，6-四磷酸不是一个必须的中间体，这与先前的模型（奥利弗，K. G.，Putney，J.W.，小的，奥比，J.F.，和Shears，S. B。（1992）J.Biol.Chem.267，21528-21534）。肌醇1，3，4，6-四磷酸3-激酶可被肌醇1，4，5，6-四磷酸抑制（IC 50，1 μ M）。用阴离子交换层析法分离了可溶性1，4，5，6-四磷酸肌醇3-激酶和1，4，5-三磷酸肌醇3-激酶。此外，从大鼠和人脑中获得的两种肌醇1，4，5-三磷酸3-激酶同工酶的cDNA克隆不磷酸化肌醇1，4，5，6-四磷酸。因此，这两种3-激酶活性由不同的酶进行。
Liver homogenates phosphorylated inositol 1,4,5,6-tetrakisphosphate exclusively to inositol 1,3,4,5,6-pentakisphosphate. Approximately 30% of this phosphorylating activity was associated with the particulate fraction of the cell, in contrast to the inositol 3,4,5,6-tetrakisphosphate 1-kinase, which was 90% soluble. This soluble 1-kinase activity was resolved from the soluble activity that phosphorylated inositol 1,4,5,6-tetrakisphosphate by anion-exchange chromatography. The two phosphorylating activities were also found to be differentially inhibited by inositol 1,3,4-trisphosphate (IC50 for 3-kinase > 100 microM; IC50 for 1-kinase < 1 microM). Thus, we have demonstrated that inositol 1,4,5,6-tetrakisphosphate is phosphorylated directly by a 3-kinase, and inositol 3,4,5,6-tetrakisphosphate is not an obligatory intermediate, in contrast to one previous model (Oliver, K. G., Putney, J. W., Jr., Obie, J. F., and Shears, S. B. (1992) J. Biol. Chem. 267, 21528-21534). Inositol 1,4,5,6-tetrakisphosphate 3-kinase was inhibited by inositol 1,3,4,6-tetrakisphosphate (IC50, 1 microM). Soluble inositol 1,4,5,6-tetrakisphosphate 3-kinase and inositol 1,4,5-trisphosphate 3-kinase were resolved by anion-exchange chromatography. Furthermore, cDNA clones of two isozymes of inositol 1,4,5-trisphosphate 3-kinase from rat and human brain did not phosphorylate inositol 1,4,5,6-tetrakisphosphate. Thus, these two 3-kinase activities are performed by distinct enzymes.