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

Nahoko Sakaguchi, Hisako Muramatsu, Keiko Ichihara-Tanaka, Nobuaki Maeda, Masaharu Noda, Tokuo Yamamoto, Makoto Michikawa, Shinya Ikematsu, Sadatoshi Sakuma, Takashi Muramatsu

Research output: Contribution to journalArticlepeer-review

55 Citations (Scopus)

Abstract

Midkine (MK), a heparin-binding growth factor, suppresses apoptosis of embryonic neurons in culture, induced by serum deprivation. Receptor-type protein tyrosine phosphatase ζ (PTP ζ) 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 ζ, 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 ζ. 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.

Original languageEnglish
Pages (from-to)219-224
Number of pages6
JournalNeuroscience Research
Volume45
Issue number2
DOIs
Publication statusPublished - 2003 Feb 1

Keywords

  • Apoptosis
  • Chondroitin sulfate proteoglycan
  • LRP6
  • Low density lipoprotein receptor-related protein
  • Midkine
  • Receptor-type protein tyrosine phosphatase ζ

ASJC Scopus subject areas

  • Neuroscience(all)

Fingerprint Dive into the research topics of 'Receptor-type protein tyrosine phosphatase ζ as a component of the signaling receptor complex for midkine-dependent survival of embryonic neurons'. Together they form a unique fingerprint.

Cite this