Department of Chemistry, University of Illinois, Chicago, Illinois 60607.
Department of Chemistry, University of Illinois, Chicago, Illinois 60607.
J Biol Chem. 2011 Dec 2;286(48):41265-41272. doi: 10.1074/jbc.M111.300806. Epub 2011 Oct 4.
3-Phosphoinositide-dependent kinase-1 (PDK1) is a ubiquitously expressed serine/threonine kinase that functions downstream of phosphoinositide 3-kinase. Although binding of 3'-phosphoinositides, phosphatidylinositol 3,4,5-trisphosphate and phosphatidylinositol 3,4-bisphosphate, to the pleckstrin homology (PH) domain of PDK1 is known to be essential for its interaction with and activation of downstream kinases, the mechanism by which PDK1 is recruited to the plasma membrane remains controversial. Our surface plasmon resonance analysis of the PDK1 PH domain and selected mutants shows that the PH domain specifically binds phosphatidylserine using a site that is separate from the canonical phosphoinositide-binding site. Further cell studies show that this specific phosphatidylserine binding is important for the plasma membrane localization and signaling function of PDK1.
3-磷酸肌醇依赖性激酶-1（PDK1）是一种普遍表达的丝氨酸/苏氨酸激酶，其作用于磷酸肌醇 3-激酶的下游。尽管 3'-磷酸肌醇、磷脂酰肌醇 3,4,5-三磷酸和磷脂酰肌醇 3,4-二磷酸与 PDK1 的 pleckstrin 同源（PH）结构域的结合对于其与下游激酶的相互作用和激活是必需的，但是 PDK1 被招募到质膜的机制仍然存在争议。我们对 PDK1 PH 结构域和选定突变体的表面等离子体共振分析表明，PH 结构域使用与经典磷酸肌醇结合位点分离的位点特异性结合磷脂酰丝氨酸。进一步的细胞研究表明，这种特定的磷脂酰丝氨酸结合对于 PDK1 的质膜定位和信号转导功能很重要。
