Btk-dependent regulation of phosphoinositide synthesis
Btk-dependent regulation of phosphoinositide synthesis
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DOI：
10.1042/bst0320326
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发表时间：
2004-04-01
影响因子：
3.9
通讯作者：
Carpenter, CL
中科院分区：
文献类型：
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作者：
Carpenter, CL
BCR（B细胞抗原受体）的活化刺激PtdIns（3，4，5）P-3和Ins（1，4，5）P-3的产生。PtdIns（3，4，5）P-3和Ins（1，4，5）P-3由共同的底物PtdIns（4，5）P2生成。在某些系统中，连续的Ptdins（4，5）P-2合成对于最大化的Ins（1，4，5）P-3生成是必需的，但是对于BCR是否如此，以及PtdIns（4，5）P-2的合成是否在BCR激活后被调节，尚不清楚。我们发现Btk（布鲁顿氏酪氨酸激酶），胞质蛋白酪氨酸激酶Tec家族的成员，与合成PtdIns（4.5）P-2的酶PIP 5 Ks（磷脂酰肌醇4-磷酸5-激酶）组成性相关。Btk作为穿梭体发挥作用，将PIP 5 K带到质膜，作为刺激PtdIns（4，5）P-2合成的手段。Btk-PIP 5 K复合物似乎定位于脂筏。这种复合物提供了一种新的穿梭机制，允许Btk调节其上游激活剂磷酸肌醇3-激酶和其下游靶磷脂酶Cgamma 2所需的底物的产生。
Activation of the BCR (B cell antigen receptor) stimulates the production of both PtdIns(3,4,5)P-3 and Ins(1,4,5)P-3. PtdIns(3,4,5)P-3 and Ins(1,4,5)P-3 are generated from a common substrate, PtdIns(4,5)P2In some systems, continuous Ptdins(4,5)P-2 synthesis is necessary for maximal Ins(1,4,5)P-3 production, but whether this is true for the BCR, and whether PtdIns(4,5)P-2 synthesis is regulated following BCR activation, are not known. we found that Btk (Bruton's tyrosine kinase), a member of the Tec family of cytoplasmic protein tyrosine kinases, is constitutively associated with PIP5Ks (phosphaticlylinositol 4-phosphate 5-kinases), the enzymes that synthesize PtdIns(4.5)P-2. Btk functions as a shuttle to bring PIP5K to the plasma membrane as a means of stimulating PtdIns(4,5)P-2 synthesis. The Btk-PIP5K complex appears to localize to lipid rafts. This complex provides a novel shuttling mechanism that allows Btk to regulate the production of the substrate required by both its upstream activator phosphoinositide 3-kinase and its downstream target phospholipase Cgamma2.