Andresen Bradley T, Rizzo Mark A, Shome Kuntala, Romero Guillermo
Department of Pharmacology, University of Pittsburgh, Pittsburgh, PA 15261, USA.
FEBS Lett. 2002 Oct 30;531(1):65-8. doi: 10.1016/s0014-5793(02)03483-x.
Phosphatidic acid (PA) is an important second messenger produced by the activation of numerous cell surface receptors. Recent data have suggested that PA regulates multiple cellular processes. This review addresses primarily the role of PA in the regulation of the Erk1/2 cascade pathway. A model for the regulation of Erk1/2 phosphorylation by cell surface receptors is presented. According to this model, agonists stimulate the binding of GTP to Ras and the activation of phospholipase D to generate phosphatidic acid. PA promotes the binding of cRaf-1 kinase to the membrane, where it interacts with Ras.GTP and other regulatory components of the pathway. Ras-Raf complexes remain bound to the surface of endosomes, where scaffolding complexes involving Ras, cRaf-1, MEK and Erk are formed. Complete activation and coupling of the cascade requires endocytosis, a process that is also modulated by PA.
磷脂酸（PA）是由众多细胞表面受体激活产生的一种重要的第二信使。近期数据表明，PA可调节多种细胞过程。本综述主要探讨PA在调节Erk1/2级联途径中的作用。文中提出了一个细胞表面受体调节Erk1/2磷酸化的模型。根据该模型，激动剂刺激GTP与Ras结合，并激活磷脂酶D以生成磷脂酸。PA促进cRaf-1激酶与膜结合，在膜上它与Ras.GTP及该途径的其他调节成分相互作用。Ras-Raf复合物仍结合在内体表面，在那里形成了涉及Ras、cRaf-1、MEK和Erk 的支架复合物。该级联反应的完全激活和偶联需要内吞作用，而这一过程也受PA调节。
