Wisotzkey R G, Mehra A, Sutherland D J, Dobens L L, Liu X, Dohrmann C, Attisano L, Raftery L A
Cutaneous Biology Research Center, Massachusetts General Hospital, Charlestown, MA 02129, USA.
Development. 1998 Apr;125(8):1433-45. doi: 10.1242/dev.125.8.1433.
Mothers against dpp (Mad) mediates Decapentaplegic (DPP) signaling throughout Drosophila development. Here we demonstrate that Medea encodes a MAD-related protein that functions in DPP signaling. MEDEA is most similar to mammalian Smad4 and forms heteromeric complexes with MAD. Like dpp, Medea is essential for embryonic dorsal/ventral patterning. However, Mad is essential in the germline for oogenesis whereas Medea is dispensable. In the wing primordium, loss of Medea most severely affects regions receiving low DPP signal. MEDEA is localized in the cytoplasm, is not regulated by phosphorylation, and requires physical association with MAD for nuclear translocation. Furthermore, inactivating MEDEA mutations prevent nuclear translocation either by preventing interaction with MAD or by trapping MAD/MEDEA complexes in the cytosol. Thus MAD-mediated nuclear translocation is essential for MEDEA function. Together these data show that, while MAD is essential for mediating all DPP signals, heteromeric MAD/MEDEA complexes function to modify or enhance DPP responses. We propose that this provides a general model for Smad4/MEDEA function in signaling by the TGF-beta family.
抗dpp母源蛋白（Mad）在果蝇整个发育过程中介导Decapentaplegic（DPP）信号传导。在此我们证明，Medea编码一种在DPP信号传导中起作用的与MAD相关的蛋白。MEDEA与哺乳动物的Smad4最为相似，并与MAD形成异源复合物。与dpp一样，Medea对胚胎背腹模式形成至关重要。然而，Mad在生殖系中对卵子发生至关重要，而Medea则可有可无。在翅原基中，Medea的缺失对接受低DPP信号的区域影响最为严重。MEDEA定位于细胞质中，不受磷酸化调节，并且需要与MAD进行物理结合才能进行核转运。此外，失活的MEDEA突变通过阻止与MAD的相互作用或通过将MAD/MEDEA复合物截留在细胞质中来阻止核转运。因此，MAD介导的核转运对MEDEA功能至关重要。这些数据共同表明，虽然MAD对介导所有DPP信号至关重要，但异源MAD/MEDEA复合物的功能是修饰或增强DPP反应。我们提出，这为TGF-β家族信号传导中Smad4/MEDEA的功能提供了一个通用模型。
