Abstract
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.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 300-307 |
| Number of pages | 8 |
| Journal | Biochemical and Biophysical Research Communications |
| Volume | 292 |
| Issue number | 2 |
| DOIs | |
| State | Published - 2002 |
Funding
We thank Dr. Charles O. Rock (St. Jude Children’s Research Hospital) for providing us mouse DOC-2/DAB2 cDNA. This study was supported by NIH Grants AR 41653 and GM 55834.
Keywords
- ATPase
- Actin
- DOC-2/DAB2
- Molecular motor
- Myosin VI
- Rab2
- Ras
- Trafficking
- Vesicle transport
ASJC Scopus subject areas
- Molecular Biology
- Biophysics
- Biochemistry
- Cell Biology