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

Research output: Contribution to journalArticlepeer-review

425 Scopus citations


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
Issue number18
StatePublished - 1995
Externally publishedYes

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology


Dive into the research topics of 'Cardiotrophin-1. Biological activities and binding to the leukemia inhibitory factor receptor/gp130 signaling complex'. Together they form a unique fingerprint.

Cite this