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.

Receptor-type protein tyrosine phosphatase zeta as a component of the signaling receptor complex for midkine-dependent survival of embryonic neurons.

Midkine (MK), a heparin-binding growth factor, suppresses apoptosis of embryonic neurons in culture, induced by serum deprivation. Receptor-type protein tyrosine phosphatase zeta (PTP zeta) is a chondroitin sulfate proteoglycan with a transmembrane domain and intracellular tyrosine phosphatase domains. The activity of MK was abolished by digestion with chondroitinase ABC, or addition of the antibody to PTP zeta, while digestion with heparitinase showed no significant effect.