Karandikar M, Xu S, Cobb M H
Department of Pharmacology, University of Texas Southwestern Medical Center, Dallas, Texas 75390-9041, USA.
J Biol Chem. 2000 Dec 22;275(51):40120-7. doi: 10.1074/jbc.M005926200.
Mitogen-activated protein (MAP) kinase cascades are involved in transmitting signals that are generated at the cell surface into the cytosol and nucleus and consist of three sequentially acting enzymes: a MAP kinase, an upstream MAP/extracellular signal-regulated protein kinase (ERK) kinase (MEK), and a MEK kinase (MEKK). Protein-protein interactions within these cascades provide a mechanism to control the localization and function of the proteins. MEKK1 is implicated in activation of the c-Jun N-terminal kinase/stress-activated protein kinase (JNK/SAPK) and ERK1/2 MAP kinase pathways. We showed previously that MEKK1 binds directly to JNK/SAPK. In this study we demonstrate that endogenous MEKK1 binds to endogenous ERK2, MEK1, and another MEKK level kinase, Raf-1, suggesting that it can assemble all three proteins of the ERK2 MAP kinase module.
丝裂原活化蛋白（MAP）激酶级联反应参与将细胞表面产生的信号传递至细胞质和细胞核，它由三种依次作用的酶组成：一种MAP激酶、一种上游MAP/细胞外信号调节蛋白激酶（ERK）激酶（MEK）和一种MEK激酶（MEKK）。这些级联反应中的蛋白质-蛋白质相互作用提供了一种控制蛋白质定位和功能的机制。MEKK1与c-Jun氨基末端激酶/应激激活蛋白激酶（JNK/SAPK）和ERK1/2 MAP激酶途径的激活有关。我们之前表明MEKK1直接与JNK/SAPK结合。在本研究中，我们证明内源性MEKK1与内源性ERK2、MEK1以及另一种MEKK水平的激酶Raf-1结合，这表明它可以组装ERK2 MAP激酶模块的所有三种蛋白质。
