Cardiotrophin-1. Biological activities and binding to the leukemia inhibitory factor receptor/gp130 signaling complex

D. Pennica, K. J. Shaw, T. A. Swanson, M. W. Moore, D. L. Shelton, K. A. Zioncheck, A. Rosenthal, T. Taga, N. F. Paoni, W. I. Wood

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410 Scopus citations

Abstract

Cardiotrophin-1 (CT-1) is a newly isolated cytokine that was identified based on its ability to induce cardiac myocyte hypertrophy. It is a member of the family of cytokines that includes interleukins-6 and -11, leukemia inhibitory factor (LIF), ciliary neurotrophic factor, and oncostatin M. These cytokines induce a pleiotropic set of growth and differentiation activities via receptors that use a common signaling subunit, gp130. In this work we determine the activity of CT-1 in six in vitro biological assays and examine the composition of its cell surface receptor. We find that CT-1 is inactive in stimulating the growth of the hybridoma cell line, B9 and inhibits the growth of the mouse myeloid leukemia cell line, M1. CT-1 induces a phenotypic switch in rat sympathetic neurons and promotes the survival of rat dopaminergic and chick ciliary neurons. CT-1 also inhibits the differentiation of mouse embryonic stem cells. CT-1 and LIF cross-compete for binding to M1 cells, K(d) [CT-1] ~0.7 nM, and this binding is inhibited by an anti-gp130 monoclonal antibody. Both ligands can be specifically cross- linked to a protein on M1 cells with the mobility of the LIF receptor (~200 kDa). In addition, CT-1 binds directly to a purified, soluble form of the LIF receptor in solution (K(d) ~2 nM). These data show that CT-1 has a wide range of hematopoietic, neuronal, and developmental activities and that it can act via the LIF receptor and the gp130 signaling subunit.

Original languageEnglish (US)
Pages (from-to)10915-10922
Number of pages8
JournalJournal of Biological Chemistry
Volume270
Issue number18
DOIs
StatePublished - Jan 1 1995
Externally publishedYes

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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    Pennica, D., Shaw, K. J., Swanson, T. A., Moore, M. W., Shelton, D. L., Zioncheck, K. A., Rosenthal, A., Taga, T., Paoni, N. F., & Wood, W. I. (1995). Cardiotrophin-1. Biological activities and binding to the leukemia inhibitory factor receptor/gp130 signaling complex. Journal of Biological Chemistry, 270(18), 10915-10922. https://doi.org/10.1074/jbc.270.18.10915