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Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)

alpha4beta1- and alpha6beta1-integrins are functional receptors for midkine, a heparin-binding growth factor.

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 zeta, low-density-lipoprotein-receptor-related protein and anaplastic lymphoma kinase have been identified as receptors for midkine. We found beta1 integrin in midkine- binding proteins from 13-day-old mouse embryos. beta1-Integrin bound to a midkine-agarose column and was eluted mostly with EDTA. Further study revealed that the alpha-subunits capable of binding to midkine were alpha4 and alpha6. Purified alpha4beta1- and alpha6beta1-integrins bound midkine. Anti-alpha4 antibody inhibited the midkine-dependent migration of osteoblastic cells, and anti-alpha6 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 alpha4beta1- and alpha6beta1-integrins are functional receptors for midkine. We observed that the low-density-lipoprotein-receptor-related-protein-6 ectodomain was immunoprecipitated with alpha6beta1-integrin and alpha4beta1-integrin. The low-density-lipoprotein-receptor-related-protein-6 ectodomain was also immunoprecipitated with receptor-type protein tyrosine phosphatase zeta. alpha4beta1- and alpha6beta1-Integrins are expected to co-operate with other midkine receptors, possibly in a multimolecular complex that contains other midkine receptors.[1]


  1. alpha4beta1- and alpha6beta1-integrins are functional receptors for midkine, a heparin-binding growth factor. Muramatsu, H., Zou, P., Suzuki, H., Oda, Y., Chen, G.Y., Sakaguchi, N., Sakuma, S., Maeda, N., Noda, M., Takada, Y., Muramatsu, T. J. Cell. Sci. (2004) [Pubmed]
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