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

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

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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 (US)
Pages (from-to)5405-5415
Number of pages11
JournalJournal of Cell Science
Volume117
Issue number22
DOIs
StatePublished - Oct 15 2004

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Integrins
Heparin
Intercellular Signaling Peptides and Proteins
Low Density Lipoprotein Receptor-Related Protein-6
Protein Tyrosine Phosphatases
Anti-Idiotypic Antibodies
LDL-Receptor Related Proteins
Paxillin
midkine
midkine receptors
LDL Receptors
Edetic Acid
Sepharose
Cell Movement
Tyrosine
Carrier Proteins
Embryonic Structures
Phosphorylation
Neurons
Growth

All Science Journal Classification (ASJC) codes

  • Cell Biology

Cite this

Muramatsu, H., Zou, P., Suzuki, H., Oda, Y., Chen, G., Sakaguchi, N., ... 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

α4β1- and α6β 1-integrins are functional receptors for midkine, a heparin-binding growth factor. / Muramatsu, Hisako; Zou, Peng; Suzuki, Hiromichi; Oda, Yoshihiro; Chen, Guoyun; Sakaguchi, Nahoko; Sakuma, Sadatoshi; Maeda, Nobuaki; Noda, Masaharu; Takada, Yoshikazu; Muramatsu, Takashi.

In: Journal of Cell Science, Vol. 117, No. 22, 15.10.2004, p. 5405-5415.

Research output: Contribution to journalArticle

Muramatsu, H, Zou, P, Suzuki, H, Oda, Y, Chen, G, 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, vol. 117, no. 22, pp. 5405-5415. https://doi.org/10.1242/jcs.01423
Muramatsu, Hisako ; Zou, Peng ; Suzuki, Hiromichi ; Oda, Yoshihiro ; Chen, Guoyun ; Sakaguchi, Nahoko ; Sakuma, Sadatoshi ; Maeda, Nobuaki ; Noda, Masaharu ; Takada, Yoshikazu ; Muramatsu, Takashi. / α4β1- and α6β 1-integrins are functional receptors for midkine, a heparin-binding growth factor. In: Journal of Cell Science. 2004 ; Vol. 117, No. 22. pp. 5405-5415.
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