A TIGHTLY ASSOCIATED SERINE THREONINE PROTEIN-KINASE REGULATES PHOSPHOINOSITIDE 3-KINASE ACTIVITY
A TIGHTLY ASSOCIATED SERINE THREONINE PROTEIN-KINASE REGULATES PHOSPHOINOSITIDE 3-KINASE ACTIVITY
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DOI：
10.1128/mcb.13.3.1657
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发表时间：
1993-03-01
影响因子：
5.3
通讯作者：
CANTLEY, LC
中科院分区：
文献类型：
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作者：
CARPENTER, CL;AUGER, KR;CANTLEY, LC
我们确定了一个丝氨酸/苏氨酸蛋白激酶，它与磷酸肌醇3-激酶（PtdIns 3-激酶）相关并使其磷酸化。丝氨酸激酶磷酸化PtdIns 3-激酶的85-和110-kDa亚基，并从大鼠肝脏中纯化，并与85-kDa亚基的抗体免疫沉淀。胰蛋白酶磷酸肽图谱表明，来自多瘤病毒中间T转化细胞的p85在体外由相关丝氨酸激酶磷酸化的三个位点在体内被磷酸化。PtdIns 3-激酶的85-kDa亚基在体外以每摩尔p85约1摩尔磷酸盐的化学计量在丝氨酸上磷酸化。这种磷酸化导致PtdIns 3-激酶活性降低三至七倍。用蛋白磷酸酶2A去磷酸化可逆转抑制作用。这表明蛋白磷酸酶2A与中间T抗原的结合可能具有激活PtdIns 3-激酶的功能。
We identified a serine/threonine protein kinase that is associated with and phosphorylates phosphoinositide 3-kinase (PtdIns 3-kinase). The serine kinase phosphorylates both the 85- and 110-kDa subunits of PtdIns 3-kinase and purifies with it from rat liver and immunoprecipitates with antibodies raised to the 85-kDa subunit. Tryptic phosphopeptide maps indicate that p85 from polyomavirus middle T-transformed cells is phosphorylated in vivo at three sites phosphorylated in vitro by the associated serine kinase. The 85-kDa subunit of PtdIns 3-kinase is phosphorylated in vitro on serine at a stoichiometry of approximately 1 mol of phosphate per mol of p85. This phosphorylation results in a three- to sevenfold decrease in PtdIns 3-kinase activity. Dephosphorylation with protein phosphatase 2A reverses the inhibition. This suggests that the association of protein phosphatase 2A with middle T antigen may function to activate PtdIns 3-kinase.