Flt3 ligand induces tyrosine phosphorylation of Gab1 and Gab2 and their association with Shp-2, grb2, and P13 kinase

Flt3 ligand induces tyrosine phosphorylation of Gab1 and Gab2 and their association with Shp-2, grb2, and P13 kinase
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DOI:
10.1006/bbrc.2000.3662
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发表时间:
2000-10-14
影响因子:
3.1
通讯作者:
Broxmeyer, HE
Broxmeyer, HE
中科院分区:
生物学4区
文献类型:
--
作者:
Zhang, SL;Broxmeyer, HE

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受体酪氨酸激酶Flt3已被证明在造血干细胞和祖细胞的增殖、分化和存活中发挥重要作用。虽然Fits的一些受体后信号事件已经被表征,但Gab家族蛋白在Flt3信号传导中的参与尚不清楚。在本研究中,我们发现在Flt3配体刺激Flt3配体应答细胞后,Gab1和Gab2都被快速酪氨酸磷酸化。它们与酪氨酸磷酸化的Shp-2、p85、Grb2和Shc相互作用。结果表明,Gab蛋白参与Flt3信号通路介导Shp-2和PI3激酶通路的下游激活,并可能介导Ras/Raf/MAPK通路。(C) 2000年学术出版社。
The receptor tyrosine kinase Flt3 has been shown to play an important role in proliferation, differentiation, and survival of hematopoietic stem and progenitor cells. Although some postreceptor signaling events of Fits have been characterized, the involvement of Gab family proteins in Flt3 signaling is not known, In this study, we show that both Gab1 and Gab2 are rapidly tyrosine phosphorylated after Flt3 ligand stimulation of Flt3 ligand-responsive cells. They interact with tyrosine-phosphorylated Shp-2, p85, Grb2, and Shc. The results suggest that Gab proteins are engaged in Flt3 signaling to mediate downstream activation of Shp-2 and PI3 kinase pathways and possibly the Ras/Raf/MAPK pathway. (C) 2000 Academic Press.