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

Diane Pennica, Kenneth J. Shaw, Todd Swanson, Mark W. Moore, David L. Shelton, Kimberly A. Zioncheck, Arnon Rosenthal, Tetsuya Taga, Nicholas F. Paoni, William I. Wood

Research output: Contribution to journalArticle

405 Citations (Scopus)

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 (LIP), 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, Kd [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 Ml 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 (Kd ∼ 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
StatePublished - May 5 1995
Externally publishedYes

Fingerprint

OSM-LIF Receptors
Bioactivity
Cytokines
Neurons
Rats
Growth
Cells
Oncostatin M
Interleukin-11
Ciliary Neurotrophic Factor
Leukemia Inhibitory Factor
cardiotrophin 1
Cell Line
Aptitude
Myeloid Leukemia
Hybridomas
Cardiomegaly
Cell Surface Receptors
Myeloid Cells
Stem cells

ASJC Scopus subject areas

  • Biochemistry

Cite this

Pennica, D., Shaw, K. J., Swanson, T., Moore, M. W., Shelton, D. L., Zioncheck, K. A., ... 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.

Cardiotrophin-1 : Biological activities and binding to the leukemia inhibitory factor receptor/gp130 signaling complex. / Pennica, Diane; Shaw, Kenneth J.; Swanson, Todd; Moore, Mark W.; Shelton, David L.; Zioncheck, Kimberly A.; Rosenthal, Arnon; Taga, Tetsuya; Paoni, Nicholas F.; Wood, William I.

In: Journal of Biological Chemistry, Vol. 270, No. 18, 05.05.1995, p. 10915-10922.

Research output: Contribution to journalArticle

Pennica, D, Shaw, KJ, Swanson, T, Moore, MW, Shelton, DL, Zioncheck, KA, Rosenthal, A, Taga, T, Paoni, NF & Wood, WI 1995, 'Cardiotrophin-1: Biological activities and binding to the leukemia inhibitory factor receptor/gp130 signaling complex', Journal of Biological Chemistry, vol. 270, no. 18, pp. 10915-10922.
Pennica, Diane ; Shaw, Kenneth J. ; Swanson, Todd ; Moore, Mark W. ; Shelton, David L. ; Zioncheck, Kimberly A. ; Rosenthal, Arnon ; Taga, Tetsuya ; Paoni, Nicholas F. ; Wood, William I. / Cardiotrophin-1 : Biological activities and binding to the leukemia inhibitory factor receptor/gp130 signaling complex. In: Journal of Biological Chemistry. 1995 ; Vol. 270, No. 18. pp. 10915-10922.
@article{793903c3ae9445938241f0444a7668c5,
title = "Cardiotrophin-1: Biological activities and binding to the leukemia inhibitory factor receptor/gp130 signaling complex",
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 (LIP), 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, Kd [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 Ml 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 (Kd ∼ 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.",
author = "Diane Pennica and Shaw, {Kenneth J.} and Todd Swanson and Moore, {Mark W.} and Shelton, {David L.} and Zioncheck, {Kimberly A.} and Arnon Rosenthal and Tetsuya Taga and Paoni, {Nicholas F.} and Wood, {William I.}",
year = "1995",
month = "5",
day = "5",
language = "English (US)",
volume = "270",
pages = "10915--10922",
journal = "Journal of Biological Chemistry",
issn = "0021-9258",
publisher = "American Society for Biochemistry and Molecular Biology Inc.",
number = "18",

}

TY - JOUR

T1 - Cardiotrophin-1

T2 - Biological activities and binding to the leukemia inhibitory factor receptor/gp130 signaling complex

AU - Pennica, Diane

AU - Shaw, Kenneth J.

AU - Swanson, Todd

AU - Moore, Mark W.

AU - Shelton, David L.

AU - Zioncheck, Kimberly A.

AU - Rosenthal, Arnon

AU - Taga, Tetsuya

AU - Paoni, Nicholas F.

AU - Wood, William I.

PY - 1995/5/5

Y1 - 1995/5/5

N2 - 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 (LIP), 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, Kd [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 Ml 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 (Kd ∼ 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.

AB - 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 (LIP), 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, Kd [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 Ml 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 (Kd ∼ 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.

UR - http://www.scopus.com/inward/record.url?scp=0028905072&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0028905072&partnerID=8YFLogxK

M3 - Article

C2 - 7738033

AN - SCOPUS:0028905072

VL - 270

SP - 10915

EP - 10922

JO - Journal of Biological Chemistry

JF - Journal of Biological Chemistry

SN - 0021-9258

IS - 18

ER -