Phospho-Tyrosine(s) vs. Phosphatidylinositol Binding in Shc Mediated Integrin Signaling.
Phospho-Tyrosine(s) vs. Phosphatidylinositol Binding in Shc Mediated Integrin Signaling.
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DOI：
10.4236/ajmb.2015.52003
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发表时间：
2015-04
期刊：
影响因子：
--
通讯作者：
Vinogradova O
中科院分区：
文献类型：
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作者：
Lin X;Vinogradova O
Shc衔接蛋白，尤其是其p52异构体，已被确定为活化的β3整合素酪氨酸磷酸化胞质尾区的主要信号传导伙伴。受我们近期解析的Shc PTB结构域与源自β3胞质尾区的双磷酸化肽段复合物结构的启发，我们着手研究Shc与细胞膜磷脂的相互作用。我们特别关注磷脂酰肌醇（PtdIns）及其在体外对Shc介导的整合素信号传导的影响。在此，我们展示了通过等温滴定量热法（ITC）和溶液核磁共振（NMR）方法研究得到的Shc、整合素和PtdIns之间相互作用的热力学特征及分子细节。基于这些数据，我们提出了p52 Shc在质膜胞质面与磷酸化β3整合素胞质尾区相互作用的模型。
The Shc adaptor protein, particularly its p52 isoform, has been identified as a primary signaling partner for the tyrosine(s)-phosphorylated cytoplasmic tails of activated β3 integrins. Inspired by our recent structure of the Shc PTB domain in complex with a bi-phosphorylated peptide derived from β3 cytoplasmic tail, we have initiated the investigation of Shc interaction with phospholipids of the membrane. We are particularly focused on PtdIns and their effects on Shc mediated integrin signaling in vitro. Here we present thermodynamic profiles and molecular details of the interactions between Shc, integrin, and PtdIns, all of which have been studied by ITC and solution NMR methods. A model of p52 Shc interaction with phosphorylated β3 integrin cytoplasmic tail at the cytosolic face of the plasma membrane is proposed based on these data.