Regulation of muscle growth by multiple ligands signaling through activin type II receptors

Se Jin Lee, Lori A. Reed, Monique V. Davies, Stefan Girgenrath, Mary E P Goad, Kathy N. Tomkinson, Jill F. Wright, Christopher Barker, Gregory Ehrmantraut, James Holmstrom, Betty Trowell, Barry Gertz, Man Shiow Jiang, Suzanne M. Sebald, Martin Matzuk, En Li, Li Fang Liang, Edwin Quattlebaum, Ronald L. Stotish, Neil M. Wolfman

Research output: Contribution to journalArticle

Abstract

Myostatin is a secreted protein that normally functions as a negative regulator of muscle growth. Agents capable of blocking the myostatin signaling pathway could have important applications for treating human muscle degenerative diseases as well as for enhancing livestock production. Here we describe a potent myostatin inhibitor, a soluble form of the activin type IIB receptor (ACVR2B), which can cause dramatic increases in muscle mass (up to 60% in 2 weeks) when injected into wild-type mice. Furthermore, we show that the effect of the soluble receptor is attenuated but not eliminated in Mstn-/- mice, suggesting that at least one other ligand in addition to myostatin normally functions to limit muscle growth. Finally, we provide genetic evidence that these ligands signal through both activin type II receptors, ACVR2 and ACVR2B, to regulate muscle growth in vivo.

Original languageEnglish (US)
Pages (from-to)18117-18122
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume102
Issue number50
DOIs
StatePublished - Dec 13 2005

Fingerprint

Type II Activin Receptors
Myostatin
Ligands
Muscles
Growth
Livestock

Keywords

  • Myostatin
  • TGF-β

ASJC Scopus subject areas

  • Genetics
  • General

Cite this

Lee, S. J., Reed, L. A., Davies, M. V., Girgenrath, S., Goad, M. E. P., Tomkinson, K. N., ... Wolfman, N. M. (2005). Regulation of muscle growth by multiple ligands signaling through activin type II receptors. Proceedings of the National Academy of Sciences of the United States of America, 102(50), 18117-18122. https://doi.org/10.1073/pnas.0505996102

Regulation of muscle growth by multiple ligands signaling through activin type II receptors. / Lee, Se Jin; Reed, Lori A.; Davies, Monique V.; Girgenrath, Stefan; Goad, Mary E P; Tomkinson, Kathy N.; Wright, Jill F.; Barker, Christopher; Ehrmantraut, Gregory; Holmstrom, James; Trowell, Betty; Gertz, Barry; Jiang, Man Shiow; Sebald, Suzanne M.; Matzuk, Martin; Li, En; Liang, Li Fang; Quattlebaum, Edwin; Stotish, Ronald L.; Wolfman, Neil M.

In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 102, No. 50, 13.12.2005, p. 18117-18122.

Research output: Contribution to journalArticle

Lee, SJ, Reed, LA, Davies, MV, Girgenrath, S, Goad, MEP, Tomkinson, KN, Wright, JF, Barker, C, Ehrmantraut, G, Holmstrom, J, Trowell, B, Gertz, B, Jiang, MS, Sebald, SM, Matzuk, M, Li, E, Liang, LF, Quattlebaum, E, Stotish, RL & Wolfman, NM 2005, 'Regulation of muscle growth by multiple ligands signaling through activin type II receptors', Proceedings of the National Academy of Sciences of the United States of America, vol. 102, no. 50, pp. 18117-18122. https://doi.org/10.1073/pnas.0505996102
Lee, Se Jin ; Reed, Lori A. ; Davies, Monique V. ; Girgenrath, Stefan ; Goad, Mary E P ; Tomkinson, Kathy N. ; Wright, Jill F. ; Barker, Christopher ; Ehrmantraut, Gregory ; Holmstrom, James ; Trowell, Betty ; Gertz, Barry ; Jiang, Man Shiow ; Sebald, Suzanne M. ; Matzuk, Martin ; Li, En ; Liang, Li Fang ; Quattlebaum, Edwin ; Stotish, Ronald L. ; Wolfman, Neil M. / Regulation of muscle growth by multiple ligands signaling through activin type II receptors. In: Proceedings of the National Academy of Sciences of the United States of America. 2005 ; Vol. 102, No. 50. pp. 18117-18122.
@article{a66b5d8068074185acadfec633cb853a,
title = "Regulation of muscle growth by multiple ligands signaling through activin type II receptors",
abstract = "Myostatin is a secreted protein that normally functions as a negative regulator of muscle growth. Agents capable of blocking the myostatin signaling pathway could have important applications for treating human muscle degenerative diseases as well as for enhancing livestock production. Here we describe a potent myostatin inhibitor, a soluble form of the activin type IIB receptor (ACVR2B), which can cause dramatic increases in muscle mass (up to 60{\%} in 2 weeks) when injected into wild-type mice. Furthermore, we show that the effect of the soluble receptor is attenuated but not eliminated in Mstn-/- mice, suggesting that at least one other ligand in addition to myostatin normally functions to limit muscle growth. Finally, we provide genetic evidence that these ligands signal through both activin type II receptors, ACVR2 and ACVR2B, to regulate muscle growth in vivo.",
keywords = "Myostatin, TGF-β",
author = "Lee, {Se Jin} and Reed, {Lori A.} and Davies, {Monique V.} and Stefan Girgenrath and Goad, {Mary E P} and Tomkinson, {Kathy N.} and Wright, {Jill F.} and Christopher Barker and Gregory Ehrmantraut and James Holmstrom and Betty Trowell and Barry Gertz and Jiang, {Man Shiow} and Sebald, {Suzanne M.} and Martin Matzuk and En Li and Liang, {Li Fang} and Edwin Quattlebaum and Stotish, {Ronald L.} and Wolfman, {Neil M.}",
year = "2005",
month = "12",
day = "13",
doi = "10.1073/pnas.0505996102",
language = "English (US)",
volume = "102",
pages = "18117--18122",
journal = "Proceedings of the National Academy of Sciences of the United States of America",
issn = "0027-8424",
number = "50",

}

TY - JOUR

T1 - Regulation of muscle growth by multiple ligands signaling through activin type II receptors

AU - Lee, Se Jin

AU - Reed, Lori A.

AU - Davies, Monique V.

AU - Girgenrath, Stefan

AU - Goad, Mary E P

AU - Tomkinson, Kathy N.

AU - Wright, Jill F.

AU - Barker, Christopher

AU - Ehrmantraut, Gregory

AU - Holmstrom, James

AU - Trowell, Betty

AU - Gertz, Barry

AU - Jiang, Man Shiow

AU - Sebald, Suzanne M.

AU - Matzuk, Martin

AU - Li, En

AU - Liang, Li Fang

AU - Quattlebaum, Edwin

AU - Stotish, Ronald L.

AU - Wolfman, Neil M.

PY - 2005/12/13

Y1 - 2005/12/13

N2 - Myostatin is a secreted protein that normally functions as a negative regulator of muscle growth. Agents capable of blocking the myostatin signaling pathway could have important applications for treating human muscle degenerative diseases as well as for enhancing livestock production. Here we describe a potent myostatin inhibitor, a soluble form of the activin type IIB receptor (ACVR2B), which can cause dramatic increases in muscle mass (up to 60% in 2 weeks) when injected into wild-type mice. Furthermore, we show that the effect of the soluble receptor is attenuated but not eliminated in Mstn-/- mice, suggesting that at least one other ligand in addition to myostatin normally functions to limit muscle growth. Finally, we provide genetic evidence that these ligands signal through both activin type II receptors, ACVR2 and ACVR2B, to regulate muscle growth in vivo.

AB - Myostatin is a secreted protein that normally functions as a negative regulator of muscle growth. Agents capable of blocking the myostatin signaling pathway could have important applications for treating human muscle degenerative diseases as well as for enhancing livestock production. Here we describe a potent myostatin inhibitor, a soluble form of the activin type IIB receptor (ACVR2B), which can cause dramatic increases in muscle mass (up to 60% in 2 weeks) when injected into wild-type mice. Furthermore, we show that the effect of the soluble receptor is attenuated but not eliminated in Mstn-/- mice, suggesting that at least one other ligand in addition to myostatin normally functions to limit muscle growth. Finally, we provide genetic evidence that these ligands signal through both activin type II receptors, ACVR2 and ACVR2B, to regulate muscle growth in vivo.

KW - Myostatin

KW - TGF-β

UR - http://www.scopus.com/inward/record.url?scp=29144466479&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=29144466479&partnerID=8YFLogxK

U2 - 10.1073/pnas.0505996102

DO - 10.1073/pnas.0505996102

M3 - Article

C2 - 16330774

AN - SCOPUS:29144466479

VL - 102

SP - 18117

EP - 18122

JO - Proceedings of the National Academy of Sciences of the United States of America

JF - Proceedings of the National Academy of Sciences of the United States of America

SN - 0027-8424

IS - 50

ER -