Src kinase regulates the activation of a novel FGD-1-related Cdc42 guanine nucleotide exchange factor in the signaling pathway from the endothelin A receptor to JNK
Src kinase regulates the activation of a novel FGD-1-related Cdc42 guanine nucleotide exchange factor in the signaling pathway from the endothelin A receptor to JNK
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DOI：
10.1074/jbc.m301559200
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发表时间：
2003-08-08
影响因子：
4.8
通讯作者：
Itoh, H
中科院分区：
文献类型：
--
作者：
Miyamoto, Y;Yamauchi, J;Itoh, H
小GTP酶通过在非活性（GDP结合）和活性（GTP结合）状态之间循环而充当二元开关。在细胞外信号刺激下，鸟嘌呤核苷酸交换因子（GEF）刺激GDP交换为GTP，以向小GTP酶的活性形式转移，识别下游靶标。在这里，我们表明，KIAA 0793，含有大量的序列同源性的催化Dbl同源结构域的面生殖器发育不良基因产物（FGD 1），是一个特定的环境融资Cdc 42。因此，我们暂时将其命名为FRG（FGD 1相关Cdc 42-GEF）。Src激酶直接磷酸化并激活FRG，如Vav家族GEF。此外，FRG参与从内皮素A受体到c-Jun N-末端激酶的信号传导途径，导致细胞运动的抑制。这些结果表明，FRG是Cdc 42-GEF的成员，并在G蛋白偶联受体下游的信号转导通路中发挥重要作用。
Small GTPases act as binary switches by cycling between an inactive (GDP-bound) and an active (GTP-bound) state. Upon stimulation with extracellular signals, guanine-nucleotide exchange factors ( GEFs) stimulate the exchange of GDP to GTP to shift toward the active forms of small GTPases, recognizing the downstream targets. Here we show that KIAA0793, containing substantial sequence homology with the catalytic Dbl homology domain of the faciogenital dysplasia gene product (FGD1), is a specific GEF for Cdc42. We, therefore, tentatively named it FRG (FGD1-related Cdc42-GEF). Src kinase directly phosphorylates and activates FRG, as Vav family GEFs. Additionally, FRG is involved in the signaling pathway from the endothelin A receptor to c-Jun N-terminal kinase, resulting in the inhibition of cell motility. These results suggest that FRG is a member of Cdc42-GEF and plays an important role in the signaling pathway downstream of G protein-coupled receptors.