α4β1- and α6β1-integrins are functional receptors for midkine, a heparin-binding growth factor

By H. Muramatsu, P. Zou, Hiromichi Suzuki, Y. Oda, Guo-Yun Chen, Nahoko Sakaguchi, S. Sakuma, N. Maeda, M. Noda, Y. Takada and 1 more. Journal of Cell Science, 2004

123 citations recorded by the source corpus.

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 β1 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 α4β1- 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 α6β1-Integrins are expected to co-operate with other midkine receptors, possibly in a multimolecular complex that contains other midkine receptors.

Subfields: Cell Biology, Immunology and Allergy, Molecular Biology

View Paper: https://www.semanticscholar.org/paper/72f2e304d7d030de9a39b8e014c3d4a01abb899a