蛋白激酶 D1 介导的磷酸化调节血管扩张刺激磷蛋白（VASP）的定位和细胞迁移。
Protein kinase D1-mediated phosphorylations regulate vasodilator-stimulated phosphoprotein (VASP) localization and cell migration.
机构信息
Department of Cancer Biology, Mayo Clinic Comprehensive Cancer Center, Mayo Clinic, Jacksonville, Florida 32224, USA.
出版信息
J Biol Chem. 2013 Aug 23;288(34):24382-93. doi: 10.1074/jbc.M113.474676. Epub 2013 Jul 11.
Abstract
Enabled/Vasodilator-stimulated phosphoprotein (Ena/VASP) protein family members link actin dynamics and cellular signaling pathways. VASP localizes to regions of dynamic actin reorganization such as the focal adhesion contacts, the leading edge or filopodia, where it contributes to F-actin filament elongation. Here we identify VASP as a novel substrate for protein kinase D1 (PKD1). We show that PKD1 directly phosphorylates VASP at two serine residues, Ser-157 and Ser-322. These phosphorylations occur in response to RhoA activation and mediate VASP re-localization from focal contacts to the leading edge region. The net result of this PKD1-mediated phosphorylation switch in VASP is increased filopodia formation and length at the leading edge. However, such signaling when persistent induced membrane ruffling and decreased cell motility.
摘要
Ena/VASP 蛋白家族成员将肌动蛋白动力学和细胞信号通路联系起来。VASP 定位于动态肌动蛋白重排的区域，如粘着斑接触、前缘或丝状伪足，在这些区域它有助于 F-肌动蛋白丝的延伸。在这里，我们发现 VASP 是蛋白激酶 D1 (PKD1) 的一个新底物。我们表明 PKD1 可直接在丝氨酸残基 157 和 322 上磷酸化 VASP。这些磷酸化反应发生在 RhoA 激活的响应中，并介导 VASP 从粘着斑重新定位到前缘区域。PKD1 介导的 VASP 磷酸化转换的净结果是增加了前缘处的丝状伪足形成和长度。然而，当这种信号持续存在时，会诱导细胞膜皱襞和降低细胞迁移。
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2
Protein kinase D regulates RhoA activity via rhotekin phosphorylation.
J Biol Chem. 2012 Mar 16;287(12):9473-83. doi: 10.1074/jbc.M112.339564. Epub 2012 Jan 6.
3
Protein kinase D regulates cofilin activity through p21-activated kinase 4.
J Biol Chem. 2011 Sep 30;286(39):34254-61. doi: 10.1074/jbc.M111.259424. Epub 2011 Aug 9.
4
A novel protein kinase D phosphorylation site in the tumor suppressor Rab interactor 1 is critical for coordination of cell migration.
Mol Biol Cell. 2011 Mar 1;22(5):570-80. doi: 10.1091/mbc.E10-05-0427. Epub 2011 Jan 5.
5
Protein kinase D controls actin polymerization and cell motility through phosphorylation of cortactin.
J Biol Chem. 2010 Jun 11;285(24):18672-83. doi: 10.1074/jbc.M109.093880. Epub 2010 Apr 2.
6
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J Cell Sci. 2009 Nov 1;122(Pt 21):3954-65. doi: 10.1242/jcs.044537. Epub 2009 Oct 13.
7
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Cancer Res. 2009 Jul 15;69(14):5634-8. doi: 10.1158/0008-5472.CAN-09-0718. Epub 2009 Jun 30.
8
Ena/VASP: towards resolving a pointed controversy at the barbed end.
J Cell Sci. 2009 Jun 15;122(Pt 12):1947-53. doi: 10.1242/jcs.038125.
9
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Nat Cell Biol. 2009 May;11(5):545-56. doi: 10.1038/ncb1861. Epub 2009 Mar 29.
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