Akt对ACAP1的磷酸化作用调节整合素β1的刺激依赖性再循环,以控制细胞迁移。

Phosphorylation of ACAP1 by Akt regulates the stimulation-dependent recycling of integrin beta1 to control cell migration.

作者信息

Li Jian, Ballif Bryan A, Powelka Aimee M, Dai Jun, Gygi Steven P, Hsu Victor W

机构信息

Division of Rheumatology, Immunology, and Allergy, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts 02115, USA.

出版信息

Dev Cell. 2005 Nov;9(5):663-73. doi: 10.1016/j.devcel.2005.09.012.

Abstract

Components of intracellular signaling that mediate the stimulation-dependent recycling of integrins are being identified, but key transport effectors that are the ultimate downstream targets remain unknown. ACAP1 has been shown recently to function as a transport effector in the cargo sorting of transferrin receptor (TfR) that undergoes constitutive recycling. We now show that ACAP1 also participates in the regulated recycling of integrin beta1 to control cell migration. However, in contrast to TfR recycling, the role of ACAP1 in beta1 recycling requires its phosphorylation by Akt, which is, in turn, regulated by a canonical signaling pathway. Disrupting the activities of either ACAP1 or Akt, or their assembly with endosomal beta1, inhibits beta1 recycling and cell migration. These findings advance an understanding of how integrin recycling is achieved during cell migration, and also address a basic issue of how intracellular signaling can interface with transport to achieve regulated recycling.

摘要

介导整合素刺激依赖性再循环的细胞内信号传导成分正在被识别,但作为最终下游靶点的关键转运效应器仍然未知。最近研究表明,ACAP1在经历组成型再循环的转铁蛋白受体(TfR)的货物分选过程中作为一种转运效应器发挥作用。我们现在表明,ACAP1也参与整合素β1的调节性再循环以控制细胞迁移。然而,与TfR再循环不同,ACAP1在β1再循环中的作用需要其被Akt磷酸化,而Akt又受经典信号通路调节。破坏ACAP1或Akt的活性,或它们与内体β1的组装,会抑制β1再循环和细胞迁移。这些发现推进了我们对细胞迁移过程中整合素再循环如何实现的理解,也解决了细胞内信号传导如何与转运相互作用以实现调节性再循环这一基本问题。

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