Role of TAK1 and TAB1 in BMP signaling in early Xenopus development
Role of TAK1 and TAB1 in BMP signaling in early Xenopus development
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DOI：
10.1093/emboj/17.4.1019
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发表时间：
1998-02-16
期刊：
影响因子：
11.4
通讯作者：
Ueno, N
中科院分区：
文献类型：
--
作者：
Shibuya, H;Iwata, H;Ueno, N
转化生长因子- β (tgf - β)超家族成员通过刺激丝氨酸/苏氨酸激酶受体引发信号，最近对该信号通路的研究发现了两种新型介导分子，Smads和tgf - β活化激酶I （TAK1）。Smads可以模拟骨形态发生蛋白（BMP）、激活素和tgf - β的作用，其中TAK1和TAB1分别被鉴定为MAPKKK及其激活因子，可能参与tgf - β超家族诱导的基因表达上调，但其生物学作用尚不清楚。在此，我们研究了TAK1和TAB1在爪蟾早期胚胎背腹侧模式中的作用，爪蟾TAK1 （xTAK1）异位表达在早期胚胎诱导细胞死亡中的作用。然而，有趣的是，bcl-2与活化形式的xTAK1或xTAK1和xTAB1在背侧卵裂球中同时过表达不仅可以挽救细胞，还可以引起胚胎的腹侧化。此外，已知抑制内源性信号传导的激酶阴性形式的xTAK1 （xTAK1KN）可以部分挽救由组成性活性的BMP-2/4型IA受体（BMPR-IA）表达产生的表型。此外，xTAK1KN可阻断Smad1或5诱导的腹侧中胚层标记基因的表达，提示xTAK1和xTAB1协同参与爪蟾胚胎BMP信号转导通路。
Transforming growth factor-beta (TGF-beta) superfamily members elicit signals through stimulation of serine/threonine kinase receptors, Recent studies of this signaling pathway have identified two types of novel mediating molecules, the Smads and TGF-beta activated kinase I (TAK1). Smads were shown to mimic the effects of bone morphogenetic protein (BMP), activin and TGF-beta, TAK1 and TAB1 were identified as a MAPKKK and its activator, respectively, which might be involved in the up-regulation of TGF-beta superfamily-induced gene expression, but their biological role is poorly understood, Here, we have examined the role of TAK1 and TAB1 in the dorsoventral patterning of early Xenopus embryos, Ectopic expression of Xenopus TAK1 (xTAK1) in early embryos induced cell death, Interestingly, however, concomitant overexpression of bcl-2 with the activated form of xTAK1 or both xTAK1 and xTAB1 in dorsal blastomeres not only rescued the cells but also caused the ventralization of the embryos, In addition, a kinase-negative form of xTAK1 (xTAK1KN) which is known to inhibit endogenous signaling could partially rescue phenotypes generated by the expression of a constitutively active BMP-2/4 type IA receptor (BMPR-IA). Moreover, xTAK1KN could block the expression of ventral mesoderm marker genes induced by Smad1 or 5, These results thus suggest that xTAK1 and xTAB1 function in the BMP signal transduction pathway in Xenopus embryos in a cooperative manner.