α4β1- and α6β 1-integrins are functional receptors for midkine, a heparin-binding growth factor

Hisako Muramatsu, Peng Zou, Hiromichi Suzuki, Yoshihiro Oda, Guo Yun Chen, Nahoko Sakaguchi, Sadatoshi Sakuma, Nobuaki Maeda, Masaharu Noda, Yoshikazu Takada, Takashi Muramatsu

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96 Citations (Scopus)

Abstract

Midkine is a heparin-binding growth factor that promotes the growth, survival, migration and differentiation of various target cells. So far, receptor-type protein tyrosine phosphatase ζ, low-density-lipoprotein-receptor-related protein and anaplastic lymphoma kinase have been identified as receptors for midkine. We found β 1 integrin in midkine-binding proteins from 13-day-old mouse embryos. β1-Integrin bound to a midkine-agarose column and was eluted mostly with EDTA. Further study revealed that the α-subunits capable of binding to midkine were α4 and α6. Purified α4β1- and α6β1-integrins bound midkine. Anti-α4 antibody inhibited the midkine-dependent migration of osteoblastic cells, and anti-α6 antibody inhibited the midkine-dependent neurite outgrowth of embryonic neurons. After midkine treatment, tyrosine phosphorylation of paxillin, an integrin-associated molecule, was transiently increased in osteoblastic cells. Therefore, we concluded that α4β 1- and α6β1-integrins are functional receptors for midkine. We observed that the low-density-lipoprotein-receptor-related-protein-6 ectodomain was immunoprecipitated with α6β1-integrin and α4β1-integrin. The low-density-lipoprotein-receptor-related-protein-6 ectodomain was also immunoprecipitated with receptor-type protein tyrosine phosphatase ζ. α4β1- and α6β 1-Integrins are expected to co-operate with other midkine receptors, possibly in a multimolecular complex that contains other midkine receptors.

Original languageEnglish
Pages (from-to)5405-5415
Number of pages11
JournalJournal of Cell Science
Volume117
Issue number22
DOIs
Publication statusPublished - Oct 15 2004
Externally publishedYes

Keywords

  • Cell migration
  • Growth factor
  • Integrin
  • LDL-receptor related protein
  • Midkine

ASJC Scopus subject areas

  • Cell Biology

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    Muramatsu, H., Zou, P., Suzuki, H., Oda, Y., Chen, G. Y., Sakaguchi, N., Sakuma, S., Maeda, N., Noda, M., Takada, Y., & Muramatsu, T. (2004). α4β1- and α6β 1-integrins are functional receptors for midkine, a heparin-binding growth factor. Journal of Cell Science, 117(22), 5405-5415. https://doi.org/10.1242/jcs.01423