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

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. [Display omitted] •Extracts of marine invertebrates stimulate proliferation of Ba/F3 cells expressed with thrombopoietin receptor (c-Mpl).•A novel sponge derived 14 kDa protein thrombocorticin potently activated c-Mpl.•Thrombocorticin is the first example of exogenous protein that activates c-Mpl.•The activation by thrombocorticin was mediated by Jak/STAT signaling pathway.