Howard Hughes Medical Institute and Department of Biological Chemistry, University of California, Los Angeles, CA 90095-1662, USA.
Sci Signal. 2011 Oct 11;4(194):ra68. doi: 10.1126/scisignal.2002034.
Bone morphogenetic proteins (BMPs) and Wnts are growth factors that provide essential patterning signals for cell proliferation and differentiation. Here, we describe a molecular mechanism by which the phosphorylation state of the Drosophila transcription factor Mad determines its ability to transduce either BMP or Wingless (Wg) signals. Previously, Mad was thought to function in gene transcription only when phosphorylated by BMP receptors. We found that the unphosphorylated form of Mad was required for canonical Wg signaling by interacting with the Pangolin-Armadillo transcriptional complex. Phosphorylation of the carboxyl terminus of Mad by BMP receptor directed Mad toward BMP signaling, thereby preventing Mad from functioning in the Wg pathway. The results show that Mad has distinct signal transduction roles in the BMP and Wnt pathways depending on its phosphorylation state.
骨形态发生蛋白（BMPs）和 Wnts 是生长因子，为细胞增殖和分化提供必需的模式信号。在这里，我们描述了一种分子机制，通过该机制，果蝇转录因子 Mad 的磷酸化状态决定了其传递 BMP 或 Wingless（Wg）信号的能力。以前，Mad 被认为仅在被 BMP 受体磷酸化时才在基因转录中发挥作用。我们发现，未磷酸化的 Mad 形式通过与 Pangolin-Armadillo 转录复合物相互作用，对于经典的 Wg 信号是必需的。Mad 的羧基末端被 BMP 受体磷酸化后，Mad 就会向 BMP 信号转导，从而阻止 Mad 在 Wg 途径中发挥作用。结果表明，Mad 根据其磷酸化状态在 BMP 和 Wnt 途径中具有不同的信号转导作用。
