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

Research output: Contribution to journalArticle

94 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

Fingerprint

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

Keywords

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

ASJC Scopus subject areas

  • Cell Biology

Cite this

Muramatsu, H., Zou, P., Suzuki, H., Oda, Y., Chen, G. Y., 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, Guo Yun; 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, GY, 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, Guo Yun ; 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.
@article{989c20f3414543d1b9a9aa9adcc570d0,
title = "α4β1- and α6β 1-integrins are functional receptors for midkine, a heparin-binding growth factor",
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.",
keywords = "Cell migration, Growth factor, Integrin, LDL-receptor related protein, Midkine",
author = "Hisako Muramatsu and Peng Zou and Hiromichi Suzuki and Yoshihiro Oda and Chen, {Guo Yun} and Nahoko Sakaguchi and Sadatoshi Sakuma and Nobuaki Maeda and Masaharu Noda and Yoshikazu Takada and Takashi Muramatsu",
year = "2004",
month = "10",
day = "15",
doi = "10.1242/jcs.01423",
language = "English",
volume = "117",
pages = "5405--5415",
journal = "Journal of Cell Science",
issn = "0021-9533",
publisher = "Company of Biologists Ltd",
number = "22",

}

TY - JOUR

T1 - α4β1- and α6β 1-integrins are functional receptors for midkine, a heparin-binding growth factor

AU - Muramatsu, Hisako

AU - Zou, Peng

AU - Suzuki, Hiromichi

AU - Oda, Yoshihiro

AU - Chen, Guo Yun

AU - Sakaguchi, Nahoko

AU - Sakuma, Sadatoshi

AU - Maeda, Nobuaki

AU - Noda, Masaharu

AU - Takada, Yoshikazu

AU - Muramatsu, Takashi

PY - 2004/10/15

Y1 - 2004/10/15

N2 - 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.

AB - 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.

KW - Cell migration

KW - Growth factor

KW - Integrin

KW - LDL-receptor related protein

KW - Midkine

UR - http://www.scopus.com/inward/record.url?scp=9444262481&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=9444262481&partnerID=8YFLogxK

U2 - 10.1242/jcs.01423

DO - 10.1242/jcs.01423

M3 - Article

C2 - 15466886

AN - SCOPUS:9444262481

VL - 117

SP - 5405

EP - 5415

JO - Journal of Cell Science

JF - Journal of Cell Science

SN - 0021-9533

IS - 22

ER -