Regulation of the interaction between PIPKI gamma and talin by proline-directed protein kinases.

Regulation of the interaction between PIPKI gamma and talin by proline-directed protein kinases.
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DOI:
10.1083/jcb.200409028
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发表时间:
2005-02-28
期刊:
The Journal of cell biology
影响因子:
--
通讯作者:
De Camilli P
De Camilli P
中科院分区:
其他
文献类型:
--
作者:
Lee SY;Voronov S;Letinic K;Nairn AC;Di Paolo G;De Camilli P

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talin与I型磷脂酰肌醇(4)磷酸5激酶γ(PIPKIγ)的相互作用调节突触和粘着斑处PI(4,5)P2的合成。在这里,我们发现人PIPKIγ的talin结合序列内丝氨酸650(S650)的磷酸化阻断了这种相互作用。在突触中,S650在静息时被p35/Cdk 5和丝裂原活化蛋白激酶磷酸化,在刺激时被钙调磷酸酶去磷酸化。S650也是细胞周期蛋白B1/Cdk 1的底物,其在有丝分裂中的磷酸化与粘着斑解体相关。通过Src对邻近S650的酪氨酸(人PIPKIγ中的Y 649)的磷酸化显示增强PIPKIγ靶向粘着斑(Ling,K.,R.L.放大图片作者:Doughman,V. V. Iyer,A. J.凡士通,S.F. Bairstow,D.F. Mosher,医学博士Sjerier和R.A.安德森。2003. 163:1339-1349)。我们发现Y 649磷酸化并不直接刺激PIPKIγ与talin的结合,但可能通过抑制S650磷酸化而间接刺激PIPKIγ与talin的结合。相反,S650磷酸化抑制Src对Y 649的磷酸化。Y 649和S650磷酸化的相反作用可能在调节突触功能以及细胞粘附和细胞运动之间的平衡中起关键作用。
The interaction of talin with phosphatidylinositol(4) phosphate 5 kinase type Iγ (PIPKIγ) regulates PI(4,5)P2 synthesis at synapses and at focal adhesions. Here, we show that phosphorylation of serine 650 (S650) within the talin-binding sequence of human PIPKIγ blocks this interaction. At synapses, S650 is phosphorylated by p35/Cdk5 and mitogen-activated protein kinase at rest, and dephosphorylated by calcineurin upon stimulation. S650 is also a substrate for cyclin B1/Cdk1 and its phosphorylation in mitosis correlates with focal adhesion disassembly. Phosphorylation by Src of the tyrosine adjacent to S650 (Y649 in human PIPKIγ) was shown to enhance PIPKIγ targeting to focal adhesions (Ling, K., R.L. Doughman, V.V. Iyer, A.J. Firestone, S.F. Bairstow, D.F. Mosher, M.D. Schaller, and R.A. Anderson. 2003. J. Cell Biol. 163:1339–1349). We find that Y649 phosphorylation does not stimulate directly PIPKIγ binding to talin, but may do so indirectly by inhibiting S650 phosphorylation. Conversely, S650 phosphorylation inhibits Y649 phosphorylation by Src. The opposite effects of the phosphorylation of Y649 and S650 likely play a critical role in regulating synaptic function as well as the balance between cell adhesion and cell motility.
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