Ras activation of a Rac1 exchange factor, Tiam1, mediates neurotrophin-3-induced Schwann cell migration
Ras activation of a Rac1 exchange factor, Tiam1, mediates neurotrophin-3-induced Schwann cell migration
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DOI：
10.1073/pnas.0507125102
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发表时间：
2005-10-11
影响因子：
11.1
通讯作者：
Chan, JR
中科院分区：
文献类型：
--
作者：
Yamauchi, J;Miyamoto, Y;Chan, JR
在髓鞘形成开始前，内源性神经营养因子对髓鞘前雪旺细胞的迁移有正向和负向调节作用。神经营养素-3(NT3)通过TrkC受体酪氨酸激酶作用，通过Rho GTP酶rac1和CDc42刺激雪旺细胞迁移。我们先前证明了TrkC直接磷酸化并激活CDC42的鸟嘌呤核苷酸交换因子DBS，以部分介导雪旺细胞的迁移。在这里，我们确定T淋巴瘤侵袭和转移(TIAM)1是参与NT3诱导雪旺细胞迁移的rac1特异性鸟苷-核苷酸交换因子。此外，小分子GTP酶RAS和Tiam1之间的相互作用在rac1的激活中起着至关重要的作用。综上所述，这些结果表明，TrkC的NT3激活通过两个平行的信号单位RAS/Tiam1/rac1和DBS/CDc42来刺激雪旺细胞迁移，并且在RAS和rac1中，雪旺细胞迁移是由两种不同类型的小GTP酶唯一地调节的。
Endogenous neurotrophins positively and negatively regulate migration of premyelinating Schwann cells before the initiation of myelination. Neurotrophin-3 (NT3) acting through the TrkC receptor tyrosine kinase stimulates Schwann cell migration via the Rho GTPases Rac1 and Cdc42. We previously demonstrated that TrkC directly phosphorylates and activates Dbs, the guanine-nucleotide exchange factor (GEF) for Cdc42, to partially mediate Schwann cell migration. Here, we identify T lymphoma invasion and metastasis (Tiam) 1 as the Rac1-specific guanine-nucleotide exchange factor involved in NT3-induced Schwann cell migration. Furthermore, the interaction between the small GTPase Ras and Tiam1 plays an essential role in the activation of Rac1. Taken together, these results suggest that NT3 activation of TrkC stimulates Schwann cell migration through two parallel signaling units, Ras/Tiam1/Rac1 and Dbs/Cdc42, and that Schwann cell migration is uniquely regulated in the case of Ras and Rac1, by two different types of small GTPases.