Tyr-phosphorylation signals translocate RIN3, the small GTPase Rab5-GEF, to early endocytic vesicles
Tyr-phosphorylation signals translocate RIN3, the small GTPase Rab5-GEF, to early endocytic vesicles
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DOI：
10.1016/j.bbrc.2008.05.027
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发表时间：
2008-07-18
影响因子：
3.1
通讯作者：
Katada, Toshiaki
中科院分区：
文献类型：
--
作者：
Yoshikawa, Manabu;Kajiho, Hiroaki;Katada, Toshiaki
小的GTP酶Rab 5在早期包合途径中起关键作用，其激活需要鸟嘌呤核苷酸交换因子（GEFs）。Rab 5-GEF具有一个保守的VPS 9结构域，RIN 3含有Src同源2、RIN家族同源（RH）和Ras相关（RA）等结构域，被认为是一个新的Rab 5-GEF。然而，RIN 3的额外结构域的精确功能和激活机制仍然未知。在此，我们发现酪氨酸磷酸化信号参与Rab 5-GEF的激活。用过钒酸盐处理HeLa细胞使RIN 3从细胞质易位到Rab 5阳性囊泡。将这种RIN 3易位应用于缺乏RIN 3的每个结构域的各种突变体。我们目前的研究结果表明，一个Ras GT3（s）激活的酪氨酸磷酸化信号与抑制性RA结构域相互作用，导致RIN 3的活性构象作为Rab 5-GEF和RIN独特的RH结构域构成的Rab 5结合区域的GEF行动的进展。(C)2008年爱思唯尔公司All rights reserved.
The small GTPase Rab5 plays a key role in early enclocytic pathway, and its activation requires guanine-nucleotide exchange factors (GEFs). Rab5-GEFs share a conserved VPS9 domain for the GEF action, and RIN3 containing additional domains, such as Src-homology 2, RIN-family homology (RH), and Ras-association (RA), was identified as a new Rab5-GEF. However, precise functions of the additional domains and the activation mechanism of RIN3 remain unknown. Here, we found tyrosine-phosphorylation signals are involved in the Rab5-GEF activation. Treatment of HeLa cells with pervanadate translocates RIN3 from cytoplasm to the Rab5-positive vesicles. This RIN3 translocation was applied to various mutants lacking each domain of RIN3. Our present results suggest that a Ras GTPase(s) activated by tyrosine-phosphorylation signals interacts with the inhibitory RA domain, resulting in an active conformation of RIN3 as a Rab5-GEF and that RIN-unique RH domain constitutes a Rab5-binding region for the progress of GEF action. (C) 2008 Elsevier Inc. All rights reserved.