A novel sponge-derived protein thrombocorticin is a new agonist for thrombopoietin receptor

Watari H 1 , Nakajima H 1 , Atsuumi W 1 , Nakamura T 2 , Nanya T 2 , Ise Y 3 Show all authors , Sakai R 4

Affiliations 

  • 1 Hokkaido University, Graduate School and Faculty of Fisheries Sciences, 3-1-1 Minato-cho, Hakodate 041-8611, Japan
  • 2 Biological Research Laboratories, Nissan Chemical Corporation, Shiraoka-shi, Saitama 349-0294, Japan
  • 3 Centre for Marine & Coastal Studies, Universiti Sains Malaysia, USM, 11800 Penang, Malaysia
  • 4 Hokkaido University, Graduate School and Faculty of Fisheries Sciences, 3-1-1 Minato-cho, Hakodate 041-8611, Japan. Electronic address: ryu.sakai@fish.hokudai.ac.jp
Comp Biochem Physiol C Toxicol Pharmacol, 2019 Jul;221:82-88.
PMID: 30978513 DOI: 10.1016/j.cbpc.2019.04.003

Abstract

We screened 868 marine extracts in search of hematopoietic molecules resulted in findings of several extracts that proliferated Ba/F3-HuMpl cells but not the cells expressed with other hematopoietic cytokine receptors, EPO and G-CSF. Separation of the most potent extract of a Micronesian sponge Corticium sp., guided by the cell proliferation assay using Ba/F3-HuMpl cells resulted in an isolation of thrombocorticin (ThC), a novel 14 kDa protein as an active principal. ThC displayed concentration-dependent proliferation of Ba/F3-HuMpl cells, and had a stronger activity than that of eltrombopag, a small molecule drug used to treat thrombocytopenia. ThC induced phosphorylation of STAT5, suggesting that it activates Jak/STAT pathway as in the case of TPO. These results together indicated that ThC is a specific agonist for c-Mpl, although the size and shape differs largely from TPO. Here we present isolation, characterization and biological activity of ThC.

* Title and MeSH Headings from MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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