Inoue Akira, Sato Osamu, Homma Kazuaki, Ikebe Mitsuo
Department of Physiology, University of Massachusetts Medical School, 55 Lake Avenue North, Worcester, Massachusetts 01655-0127, USA.
Biochem Biophys Res Commun. 2002 Mar 29;292(2):300-7. doi: 10.1006/bbrc.2002.6636.
Myosin VI is a molecular motor that moves processively along actin filaments and is believed to play a role in cargo movement in cells. Here we found that DOC-2/DAB2, a signaling molecule inhibiting the Ras cascade, binds to myosin VI at the globular tail domain. DOC-2/DAB2 binds stoichiometrically to myosin VI with one molecule per one myosin VI heavy chain. The C-terminal 122 amino acid residues of DOC-2/DAB2, containing the Grb2 binding site, is identified to be critical for the binding to myosin VI. Actin gliding assay revealed that the binding of DOC-2/DAB2 to myosin VI can support the actin filament gliding by myosin VI, suggesting that it can function as a myosin VI anchoring molecule. The C-terminal domain but not the N-terminal domain of DOC-2/DAB2 functions as a myosin VI anchoring site. The present findings suggest that myosin VI plays a role in transporting DOC-2/DAB2, a Ras cascade signaling molecule, thus involved in Ras signaling pathways.
肌球蛋白VI是一种沿着肌动蛋白丝进行持续移动的分子马达，被认为在细胞内的货物运输中发挥作用。在此，我们发现DOC-2/DAB2，一种抑制Ras级联反应的信号分子，在球状尾部结构域与肌球蛋白VI结合。DOC-2/DAB2以化学计量的方式与肌球蛋白VI结合，每一条肌球蛋白VI重链结合一个分子。DOC-2/DAB2的C末端122个氨基酸残基，包含Grb2结合位点，被确定为与肌球蛋白VI结合的关键部位。肌动蛋白滑动实验表明，DOC-2/DAB2与肌球蛋白VI的结合能够支持肌球蛋白VI介导的肌动蛋白丝滑动，这表明它可以作为肌球蛋白VI的锚定分子发挥作用。DOC-2/DAB2的C末端结构域而非N末端结构域作为肌球蛋白VI的锚定位点发挥作用。目前的研究结果表明，肌球蛋白VI在运输Ras级联信号分子DOC-2/DAB2中发挥作用，从而参与Ras信号通路。
