Flt3配体诱导Gab1和Gab2的酪氨酸磷酸化以及它们与Shp-2、Grb2和PI3激酶的结合。

Flt3 ligand induces tyrosine phosphorylation of gab1 and gab2 and their association with shp-2, grb2, and PI3 kinase.

作者信息

Zhang S, Broxmeyer H E

机构信息

Department of Microbiology/Immunology, Indiana University School of Medicine, Indianapolis, Indiana 46202, USA.

出版信息

Biochem Biophys Res Commun. 2000 Oct 14;277(1):195-9. doi: 10.1006/bbrc.2000.3662.

DOI:10.1006/bbrc.2000.3662

PMID:11027663

Abstract

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 Flt3 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.

摘要

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、分化及存活中发挥重要作用。尽管Flt3的一些受体后信号转导事件已得到表征，但Gab家族蛋白在Flt3信号转导中的作用尚不清楚。在本研究中，我们发现Flt3配体刺激Flt3配体反应性细胞后，Gab1和Gab2均迅速发生酪氨酸磷酸化。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信号转导，介导Shp-2和PI3激酶途径的下游激活，可能还介导Ras/Raf/MAPK途径的激活。