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

First Author  Sakaguchi N Year  2003
Journal  Neurosci Res Volume  45
Issue  2 Pages  219-24
PubMed ID  12573468 Mgi Jnum  J:273584
Mgi Id  MGI:6294380 Doi  10.1016/s0168-0102(02)00226-2
Citation  Sakaguchi N, et al. (2003) Receptor-type protein tyrosine phosphatase zeta as a component of the signaling receptor complex for midkine-dependent survival of embryonic neurons. Neurosci Res 45(2):219-24
abstractText  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. These results suggested that the survival-promoting signal of MK was received by a receptor complex containing PTP zeta. Low density lipoprotein receptor-related protein (LRP) has been identified as another component of the signaling receptor. Ectodomains of two related proteins expressed on neurons, namely LRP6 and apoE receptor 2, were FLAG-tagged and examined for MK binding, using MK-agarose column. Both the ectodomains were found to exhibit calcium-dependent binding to MK. These proteins may participate in MK signaling in certain cases. The survival-promoting activity of MK was abolished by PP1, an inhibitor of src protein kinase, pertussis toxin, an inhibitor of G protein-linked signaling and sodium orthovanadate, an inhibitor of PTPs.
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