Wilson Robert, Battersby Alysia, Csiszar Agnes, Vogelsang Elisabeth, Leptin Maria
Institut für Genetik, Universität zu Köln, Weyertal 121, D-50931 Cologne, Germany.
Mol Cell Biol. 2004 Mar;24(6):2263-76. doi: 10.1128/MCB.24.6.2263-2276.2004.
Signal transduction by fibroblast growth factor (FGF) receptors in Drosophila depends upon the intracellular protein Dof, which has been proposed to act downstream of the receptors and upstream of Ras. Dof is the product of a fast-evolving gene whose vertebrate homologs, BCAP and BANK, are involved in signaling downstream of the B-cell receptor. Mapping functional domains within Dof revealed that neither of its potential interaction motifs, the ankyrin repeats and the coiled coil, is essential for the function of Dof. However, we have identified a region within the N terminus of the protein with similarity to BCAP and BANK, which we refer to as the Dof, BCAP, and BANK (DBB) motif, that it is required for FGF-dependent signal transduction and is necessary for efficient interaction of Dof with the FGF receptor Heartless. In addition, we demonstrate that Dof is phosphorylated in the presence of an activated FGF receptor and that tyrosine residues could contribute to the function of the molecule.
果蝇中,成纤维细胞生长因子(FGF)受体介导的信号转导依赖于细胞内蛋白Dof,有人提出该蛋白在受体下游、Ras上游发挥作用。Dof是一个快速进化基因的产物,其脊椎动物同源物BCAP和BANK参与B细胞受体下游的信号传导。对Dof内功能域的定位显示,其潜在的相互作用基序(锚蛋白重复序列和卷曲螺旋)对Dof的功能均非必需。然而,我们在该蛋白的N端鉴定出一个与BCAP和BANK相似的区域,我们将其称为Dof、BCAP和BANK(DBB)基序,它是FGF依赖的信号转导所必需的,也是Dof与FGF受体“无情”高效相互作用所必需的。此外,我们证明在活化的FGF受体存在的情况下Dof会被磷酸化,并且酪氨酸残基可能对该分子的功能有贡献。