普列克底物蛋白同源结构域在相交蛋白-L的Cdc42双亮氨酸重复同源结构域激活及信号传导中的作用
Role of the pleckstrin homology domain in intersectin-L Dbl homology domain activation of Cdc42 and signaling.
作者信息
Pruitt Wendy M, Karnoub Antoine E, Rakauskas A Corinne, Guipponi Michel, Antonarakis Stylianos E, Kurakin Alexei, Kay Brian K, Sondek John, Siderovski David P, Der Channing J
机构信息
Department of Pharmacology and Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599-7295, USA.
出版信息
Biochim Biophys Acta. 2003 Apr 7;1640(1):61-8. doi: 10.1016/s0167-4889(03)00002-8.
Intersectin-long (ITSN-L) contains the invariant Dbl homology (DH) and pleckstrin homology (PH) domain structure characteristic of the majority of Dbl family proteins. This strict domain topography suggests that the PH domain serves an essential, conserved function in the regulation of the intrinsic guanine nucleotide exchange activity of the DH domain. We evaluated the role of the PH domain in regulating the DH domain function of ITSN-L. Surprisingly, we found that the PH domain was dispensable for guanine nucleotide exchange activity on Cdc42 in vitro, yet the PH domain enhanced the ability of the DH domain to activate Cdc42 signaling in vivo. PH domains can interact with phosphoinositide substrates and products of phosphatidylinositol 3-kinase (PI3K). However, PI3K activation did not modulate ITSN-L DH domain function in vivo.
长型相交蛋白（ITSN-L）包含大多数Dbl家族蛋白所特有的不变双鸟苷酸交换因子同源结构域（DH）和普列克底物蛋白同源结构域（PH）。这种严格的结构域拓扑结构表明，PH结构域在调节DH结构域的内在鸟嘌呤核苷酸交换活性中发挥着重要的保守功能。我们评估了PH结构域在调节ITSN-L的DH结构域功能中的作用。令人惊讶的是，我们发现PH结构域对于体外Cdc42上的鸟嘌呤核苷酸交换活性是可有可无的，但PH结构域增强了DH结构域在体内激活Cdc42信号传导的能力。PH结构域可以与磷脂酰肌醇3激酶（PI3K）的磷酸肌醇底物和产物相互作用。然而，PI3K激活在体内并未调节ITSN-L DH结构域的功能。
Zotero 插件