Format

Send to

Choose Destination
See comment in PubMed Commons below
Cell Signal. 2014 May;26(5):1082-8. doi: 10.1016/j.cellsig.2014.01.027. Epub 2014 Feb 5.

Dock4 forms a complex with SH3YL1 and regulates cancer cell migration.

Author information

1
Laboratory of Molecular Neurobiology, Graduate School of Biostudies, Kyoto University, Yoshidakonoe-cho, Sakyo-ku, Kyoto 606-8501, Japan.
2
Laboratory of Molecular Neurobiology, Graduate School of Biostudies, Kyoto University, Yoshidakonoe-cho, Sakyo-ku, Kyoto 606-8501, Japan. Electronic address: hirokato@pharm.kyoto-u.ac.jp.

Abstract

Dock4 is a member of the Dock180 family of proteins that mediates cancer cell migration through activation of Rac. However, the regulatory mechanism of Dock4 remains unclear. In this study, we show that the C-terminal proline-rich region of Dock4 is essential for the Dock4 mediated promotion of cell migration in MDA-MB-231 breast cancer cells. We found that a phosphoinositide-binding protein SH3YL1 interacted with the C-terminal proline-rich region of Dock4. Interaction of SH3YL1 with Dock4 promoted Dock4-mediated Rac1 activation and cell migration. Mutations in the phosphoinositide-binding domain disrupted the ability of SH3YL1 to promote Dock4-mediated cell migration. In addition, depletion of SH3YL1 in MDA-MB-231 cells suppressed cell migration. Taken together, these results provide evidence for a novel and functionally important interaction between Dock4 and SH3YL1 to promote cancer cell migration by regulating Rac1 activity.

KEYWORDS:

Cell migration; Dock4; GEF; Rac1; Rho family

PMID:
24508479
DOI:
10.1016/j.cellsig.2014.01.027
[Indexed for MEDLINE]
PubMed Commons home

PubMed Commons

0 comments
How to join PubMed Commons

    Supplemental Content

    Full text links

    Icon for Elsevier Science
    Loading ...
    Support Center