REGULATION BY PHOSPHORYLATION OF REVERSIBLE ASSOCIATION OF A MYRISTOYLATED PROTEIN-KINASE-C SUBSTRATE WITH THE PLASMA-MEMBRANE
REGULATION BY PHOSPHORYLATION OF REVERSIBLE ASSOCIATION OF A MYRISTOYLATED PROTEIN-KINASE-C SUBSTRATE WITH THE PLASMA-MEMBRANE
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DOI：
10.1038/351320a0
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发表时间：
1991-05-23
期刊：
影响因子：
64.8
通讯作者：
ADEREM, A
中科院分区：
文献类型：
--
作者：
THELEN, M;ROSEN, A;ADEREM, A
蛋白激酶C（PKC）通过磷酸化膜结合底物转导受体介导的信号，然后作为特异性细胞反应的效应子1。 豆蔻酰化富含丙氨酸的C激酶底物（MARCKS）是一种特异性PKC底物，与巨噬细胞活化、神经分泌和生长因子依赖性有丝分裂有关2-5。 MARCKS的豆蔻酰化是有效结合质膜所必需的6，在质膜上它与PKC 7共定位。 在这里，我们报告说，PKC依赖的磷酸化取代MARCKS从膜，其随后的去磷酸化伴随着其与膜的重新关联。 肉豆蔻酰化蛋白的磷酸化依赖性膜附着和脱离的这种循环代表了可逆膜靶向的新机制。 由于MARCKS是钙调蛋白和肌动蛋白结合蛋白（参考文献8和J. Hartwig等人，提交的手稿），膜附着/脱离周期代表了PKC可能可逆地调节肌动蛋白-膜相互作用的机制。
PROTEIN kinase C (PKC) transduces receptor-mediated signals by phosphorylating membrane-bound substrates which then act as effectors of specific cellular responses 1. The myristoylated alanine-rich C kinase substrate (MARCKS) is a specific PKC substrate which has been implicated in macrophage activation, neurosecretion and growth factor-dependent mitogenesis 2-5. Myristoylation of MARCKS is required for effective binding to the plasma membrane 6 where it colocalizes with PKC 7. Here we report that PKC-dependent phosphorylation displaces MARCKS from the membrane and that its subsequent dephosphorylation is accompanied by its reassociation with the membrane. This cycle of phosphorylation-dependent membrane attachment and detachment of a myristoylated protein represents a novel mechanism of reversible membrane targeting. As MARCKS is a calmodulin- and actin-binding protein (ref. 8, and J. Hartwig et al., manuscript submitted), the cycle of membrane attachment/detachment represents a mechanism through which PKC might reversibly regulate actin-membrane interaction.