Abi-1-bridged tyrosine phosphorylation of VASP by Abelson kinase impairs association of VASP to focal adhesions and regulates leukaemic cell adhesion

Masahiro Maruoka, Mizuho Sato, Yunfeng Yuan, Masayoshi Ichiba, Ryosuke Fujii, Takuya Ogawa, Norihiro Ishida-Kitagawa, Tatsuo Takeya, Naoki Watanabe

    Research output: Contribution to journalArticle

    24 Citations (Scopus)

    Abstract

    Mena [mammalian Ena (Enabled)]/VASP (vasodilator-stimulated phosphoprotein) proteins are the homologues of Drosophila Ena. In Drosophila, Ena is a substrate of the tyrosine kinase DAbl (Drosophila Abl). However, the link between Abl and the Mena/VASP family is not fully understood in mammals. We previously reported that Abi-1 (Abl interactor 1) promotes phosphorylation of Mena and BCAP (B-cell adaptor for phosphoinositide 3-kinase) by bridging the interaction between c-Abl and the substrate. In the present study we have identified VASP, another member of the Mena/VASP family, as an Abi-1-bridged substrate of Abl. VASP is phosphorylated by Abl when Abi-1 is co-expressed. We also found that VASP interacted with Abi-1 both in vitro and in vivo. VASP was tyrosine-phosphorylated in Bcr-Abl-positive leukaemic cells in an Abi-1-dependent manner. Co-expression of c-Abl and Abi-1 or the phosphomimetic Y39D mutation in VASP resulted in less accumulation of VASP at focal adhesions. VASP Y39D had a reduced affinity to the proline-rich region of zyxin. Interestingly, overexpression of both phosphomimetic and unphosphorylated forms of VASP, but not wild-type VASP, impaired adhesion of K562 cells to fibronectin. These results suggest that the phosphorylation and dephosphorylation cycle of VASP by the Abi-1-bridged mechanism regulates association of VASP with focal adhesions, which may regulate adhesion of Bcr-Abl-transformed leukaemic cells.

    Original languageEnglish
    Pages (from-to)889-899
    Number of pages11
    JournalBiochemical Journal
    Volume441
    Issue number3
    DOIs
    Publication statusPublished - 2012 Feb 1

    Keywords

    • Abl interactor 1 (Abi-1)
    • Bcr-Abl
    • Leukaemic cell adhesion
    • Vasodilator-stimulated phosphoprotein
    • c-Abl

    ASJC Scopus subject areas

    • Biochemistry
    • Molecular Biology
    • Cell Biology

    Fingerprint Dive into the research topics of 'Abi-1-bridged tyrosine phosphorylation of VASP by Abelson kinase impairs association of VASP to focal adhesions and regulates leukaemic cell adhesion'. Together they form a unique fingerprint.

  • Cite this

    Maruoka, M., Sato, M., Yuan, Y., Ichiba, M., Fujii, R., Ogawa, T., Ishida-Kitagawa, N., Takeya, T., & Watanabe, N. (2012). Abi-1-bridged tyrosine phosphorylation of VASP by Abelson kinase impairs association of VASP to focal adhesions and regulates leukaemic cell adhesion. Biochemical Journal, 441(3), 889-899. https://doi.org/10.1042/BJ20110951