Annexin I is phosphorylated in the multivesicular body during the processing of the epidermal growth factor receptor.
Annexin I is phosphorylated in the multivesicular body during the processing of the epidermal growth factor receptor.
复制标题
在表皮生长因子受体的加工过程中，膜联蛋白I在多个体体中被磷酸化。
DOI：
10.1083/jcb.120.1.77
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发表时间：
1993-01
影响因子：
7.8
通讯作者：
Hopkins, C R
中科院分区：
文献类型：
--
作者：
Futter, C E;Felder, S;Schlessinger, J;Ullrich, A;Hopkins, C R
我们以前已经表明，一个活跃的表皮生长因子受体（EGF-R）激酶是必要的有效分选的EGF-R的溶酶体，我们已经表明，这发生在多泡体（MVB），在那里EGF-R被分选出回收受体被删除到内部囊泡的MVB。本研究的目的是确定与MVB相关的EGF-R激酶的底物，这可能在此分选过程中发挥作用。我们使用密度偏移技术分离MVB，并显示在含有活性EGF-R激酶的MVB中，体外磷酸化的主要底物是EGF-R本身和膜联蛋白I。膜联蛋白I以钙非依赖性方式与质膜和MVB两者相关联，但仅在MVB中可以在体外磷酸化。钙非依赖性膜联蛋白I在分离的MVB中的磷酸化将其转化为需要钙进行膜结合的形式。在具有活性EGF-R激酶的细胞中，MVB中钙非依赖性膜联蛋白I的量减少，表明磷酸化诱导的钙非依赖性转化为钙依赖性形式也发生在体内。我们的观察，以及膜联蛋白I在介导膜融合中的已知特性，表明MVB中的内向囊泡形成由EGF-R诱导，并由磷酸化膜联蛋白I介导。
We have previously shown that an active epidermal growth factor receptor (EGF-R) kinase is necessary for efficient sorting of the EGF-R to the lysosome, and we have shown that this occurs in the multivesicular body (MVB), where EGF-R are sorted away from recycling receptors by being removed to the internal vesicles of the MVB. The aim of the present study was to identify substrates of the EGF-R kinase associated with MVBs which might play a role in this sorting process. We used a density shift technique to isolate MVBs and show that the major substrates phosphorylated in vitro within MVBs which contain an active EGF-R kinase are the EGF-R itself and annexin I. Annexin I is associated with both plasma membrane and MVBs in a calcium-independent manner but can be phosphorylated in vitro only in MVBs. Phosphorylation of calcium-independent annexin I in isolated MVBs converts it to a form that requires calcium for membrane association. In cells with an active EGF-R kinase the amount of calcium-independent annexin I in MVBs is reduced, suggesting that a phosphorylation-induced conversion of the calcium independent to the calcium-dependent form also occurs in vivo. Our observations, together with the known properties of annexin I in mediating membrane fusion, suggest that inward vesiculation in MVBs is induced by the EGF-R and is mediated by phosphorylated annexin I.