Ca2+/Calmodulin Stimulates GTP Binding to the Ras-related Protein Ral-A*
Ca2+/Calmodulin Stimulates GTP Binding to the Ras-related Protein Ral-A*
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DOI：
10.1074/jbc.274.21.14525
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发表时间：
1999-05
期刊：
影响因子：
--
通讯作者：
Kai Ling Wang;B. Roufogalis
中科院分区：
文献类型：
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作者：
Kai Ling Wang;B. Roufogalis
Ral-A是Ras相关的GTP结合蛋白，被认为是Ras蛋白的下游靶点，并且参与酪氨酸激酶介导的Ras依赖性磷脂酶D活化。我们最近报道，从人红细胞膜纯化的Ral-A在其C-末端区域附近鉴定的钙调蛋白结合结构域以Ca 2+依赖性方式结合钙调蛋白（Wang，K. L.，汗，M。T.，和Roufogalis，B. D.（1997）J.Biol.Chem.272，16002-16009）。在这项研究中，我们显示了增强GTP结合Ral-A的Ca 2 +/钙调素。钙调素的刺激高达3倍是钙依赖性的，半最大激活发生在180 nm的钙调素和80 nm的游离Ca 2+浓度。本研究支持Ca ~（2+）/钙调素对Ral-A激活的调节作用，并提示Ca ~（2+）/钙调素与Ral-A蛋白的信号转导途径之间可能存在直接联系。
Ral-A is a Ras-related GTP-binding protein that has been suggested to be the downstream target of Ras proteins and is involved in the tyrosine kinase-mediated, Ras-dependent activation of phospholipase D. We reported recently that Ral-A purified from human erythrocyte membrane binds to calmodulin in a Ca2+-dependent manner at a calmodulin binding domain identified near its C-terminal region (Wang, K. L., Khan, M. T., and Roufogalis, B. D. (1997) J. Biol. Chem. 272, 16002–16009). In this study we show the enhancement of GTP binding to Ral-A by Ca2+/calmodulin. The stimulation up to 3-fold by calmodulin was Ca2+-dependent, with half-maximum activation occurring at 180 nm calmodulin and 80 nm free Ca2+ concentration. The present work supports a regulatory role of Ca2+/calmodulin for the activation of Ral-A and suggests a possible direct link between signal transduction pathways of Ca2+/calmodulin and Ral-A proteins.