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.
authors.affiliation: Department of Molecular Biology and Genetics, The Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA. sjlee@jhmi.edu
authors.forename: Se-Jin
authors.initials: SJ
authors.lastname: Lee
authors.forename: Lori A
authors.initials: LA
authors.lastname: Reed
authors.forename: Monique V
authors.initials: MV
authors.lastname: Davies
authors.forename: Stefan
authors.initials: S
authors.lastname: Girgenrath
authors.forename: Mary E P
authors.initials: ME
authors.lastname: Goad
authors.forename: Kathy N
authors.initials: KN
authors.lastname: Tomkinson
authors.forename: Jill F
authors.initials: JF
authors.lastname: Wright
authors.forename: Christopher
authors.initials: C
authors.lastname: Barker
authors.forename: Gregory
authors.initials: G
authors.lastname: Ehrmantraut
authors.forename: James
authors.initials: J
authors.lastname: Holmstrom
authors.forename: Betty
authors.initials: B
authors.lastname: Trowell
authors.forename: Barry
authors.initials: B
authors.lastname: Gertz
authors.forename: Man-Shiow
authors.initials: MS
authors.lastname: Jiang
authors.forename: Suzanne M
authors.initials: SM
authors.lastname: Sebald
authors.forename: Martin
authors.initials: M
authors.lastname: Matzuk
authors.forename: En
authors.initials: E
authors.lastname: Li
authors.forename: Li-Fang
authors.initials: LF
authors.lastname: Liang
authors.forename: Edwin
authors.initials: E
authors.lastname: Quattlebaum
authors.forename: Ronald L
authors.initials: RL
authors.lastname: Stotish
authors.forename: Neil M
authors.initials: NM
authors.lastname: Wolfman
mesh_terms: D030301:Activin Receptors, Type II / Q000235:genetics / Q000378:metabolism* / Q000494:pharmacology; D000818:Animals; D008024:Ligands; D051379:Mice; D018345:Mice, Knockout; D018482:Muscle, Skeletal / Q000187:drug effects / Q000254:growth & development*; D055435:Myostatin; D009929:Organ Size; D015398:Signal Transduction / Q000502:physiology*; D016212:Transforming Growth Factor beta / Q000037:antagonists & inhibitors*
chemical_list: D008024:Ligands; C525911:MSTN protein, human; C525912:Mstn protein, mouse; D055435:Myostatin; D016212:Transforming Growth Factor beta; D030301:Activin Receptors, Type II