Alves G, Limbourg-Bouchon B, Tricoire H, Brissard-Zahraoui J, Lamour-Isnard C, Busson D
Laboratoire Génétique du Développement et Evolution, Institut Jacques Monod, C.N.R.S., Université Paris VII, Université Paris VI, 2 place Jussieu, 75251, Paris, Cedex 05, France.
Mech Dev. 1998 Nov;78(1-2):17-31. doi: 10.1016/s0925-4773(98)00130-0.
The Fused (Fu) serine-threonine kinase and the Suppressor of fused (Su(fu)) product are part of the Hedgehog (Hh) signaling pathway both in embryos and in imaginal discs. In wing imaginal discs, the Hh signal induces Cubitus interruptus (Ci) accumulation and activates patched (ptc) and decapentaplegic (dpp) expression along the anterior/posterior (A/P) boundary. In this paper, we have examined the role of the Fu and Su(fu) proteins in the regulation of Hh target gene expression in wing imaginal discs, by using different classes of fu alleles and an amorphic Su(fu) mutation. We show that, at the A/P boundary, Fu kinase activity is involved in the maintenance of high ptc expression and in the induction of late anterior engrailed (en) expression. These combined effects can account for the modulation of Ci accumulation and for the precise localization of the Dpp morphogen stripe. In contrast, in more anterior cells which do not receive Hh signal, we show that Fu plays a role independent of its kinase function in the regulation of Ci accumulation. In these cells, Fu may be involved in the stabilization of a large protein complex which is probably responsible for the regulation of Ci cleavage and/or targeting to nucleus. We propose that the Fused function is necessary for the activation of full-length Ci and counteracts the negative Su(fu) effect on the pathway, leading to en, ptc and dpp expression.
融合（Fu）丝氨酸 - 苏氨酸激酶和融合抑制因子（Su(fu)）产物是胚胎和成虫盘中刺猬（Hh）信号通路的一部分。在翅成虫盘中，Hh信号诱导间断翅脉（Ci）积累，并沿前后（A/P）边界激活patched（ptc）和decapentaplegic（dpp）的表达。在本文中，我们通过使用不同类型的fu等位基因和一个无义的Su(fu)突变，研究了Fu和Su(fu)蛋白在翅成虫盘中对Hh靶基因表达调控中的作用。我们发现，在A/P边界，Fu激酶活性参与维持高ptc表达以及诱导晚期前engrailed（en）表达。这些综合作用可以解释Ci积累的调节以及Dpp形态发生素条纹的精确定位。相反，在未接收Hh信号的更靠前的细胞中，我们发现Fu在调节Ci积累中发挥了独立于其激酶功能的作用。在这些细胞中，Fu可能参与了一个大蛋白复合物的稳定，该复合物可能负责Ci的切割调节和/或靶向细胞核。我们提出，融合功能对于全长Ci的激活是必要的，并且抵消了Su(fu)对该通路的负向作用，从而导致en、ptc和dpp的表达。
