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首页> 外文期刊>Molecular and Cellular Biology >Abl Interactor 1 Binds to Sos and Inhibits Epidermal Growth Factor- and v-Abl-Induced Activation of Extracellular Signal-Regulated Kinases
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Abl Interactor 1 Binds to Sos and Inhibits Epidermal Growth Factor- and v-Abl-Induced Activation of Extracellular Signal-Regulated Kinases

机译：Abl相互作用因子1绑定到sos并抑制表皮生长因子和v-Abl诱导的细胞外信号调节激酶的激活。

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Recent studies have suggested that members of the Abl interactor (Abi) protein family negatively regulate cell growth and transformation. To date, however, no specific role in these cellular processes has been identified for the Abi family. Here we describe the inhibition by overexpressed Abi-1 of a mitogenic pathway activated by both growth factors and v-Abl. We have identified the guanine nucleotide exchange factors Sos1 and Sos2 as novel binding partners of Abi-1. A domain that is required for interaction with Sos in vivo has been mapped to the amino terminus of Abi-1. Overexpression of Abi-1 inhibits epidermal growth factor (EGF)-induced activation of extracellular signal-regulated kinases (Erks) but does not affect EGF-induced activation of c-Jun N-terminal kinase or Akt. In addition, overexpression of Abi-1 blocks Erk activation induced by v-Abl. In both cases, the maximal inhibitory effect requires an intact amino-terminal Sos-binding domain in Abi-1. Finally, we demonstrate that tyrosine phosphorylation of endogenous Abi-1 in fibroblasts is induced by both v-Abl and serum stimulation, further suggesting a role for Abi-1 in signal transduction initiated by v-Abl and growth factors. Taken together, these findings suggest that overexpressed Abi proteins negatively regulate cell growth and transformation by specifically targeting the Erk pathway.
机译：最近的研究表明，Abl相互作用蛋白（Abi）蛋白家族的成员会对细胞的生长和转化产生负面影响。然而，迄今为止，尚未确定Abi家族在这些细胞过程中的具体作用。在这里，我们描述了由过表达的Abi-1对由生长因子和v-Abl激活的促有丝分裂途径的抑制作用。我们已经确定鸟嘌呤核苷酸交换因子Sos1和Sos2为Abi-1的新型结合伴侣。与Sos在体内相互作用所需的结构域已定位到Abi-1的氨基末端。 Abi-1的过表达抑制表皮生长因子（EGF）诱导的细胞外信号调节激酶（Erks）的激活，但不影响EGF诱导的c-Jun N端激酶或Akt的激活。此外，Abi-1的过表达可阻断v-Abl诱导的Erk激活。在这两种情况下，最大的抑制作用都需要一个完整的Abi-1氨基末端Sos结合结构域。最后，我们证明了成纤维细胞中内源性Abi-1的酪氨酸磷酸化受到v-Abl和血清刺激的诱导，进一步暗示了Abi-1在由v-Abl和生长因子引发的信号转导中的作用。综上，这些发现表明，过表达的Abi蛋白通过特异性靶向Erk途径而负调控细胞的生长和转化。

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