Expression of growth/differentiation factor 11, a new member of the BMP/TGFβ superfamily during mouse embryogenesis

Nakashima, Mitsuyoshi; Toyono, Takashi; Akamine, Akifumi; Joyner, Alexandra L.

doi:10.1016/s0925-4773(98)00205-6

Cited by 230 publications

(214 citation statements)

References 9 publications

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“…Firstly, myostatin (GDF8) is a close structural homologue of GDF11, with 90% amino acid sequence identity shared in their mature activeforms. 40 Thus, our assay for mouse and human serum GDF11 does not distinguish circulating GDF11 and GDF8. As a result, we did not accurately determine the changes of GDF11 in mice and in human.…”

Section: Discussionmentioning

confidence: 84%

GDF11 Protects against Endothelial Injury and Reduces Atherosclerotic Lesion Formation in Apolipoprotein E-Null Mice

et al. 2016

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Section: Discussionmentioning

confidence: 84%

GDF11 Protects against Endothelial Injury and Reduces Atherosclerotic Lesion Formation in Apolipoprotein E-Null Mice

et al. 2016

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“…18), and any of these could conceivably play a similar role to myostatin in muscle. Perhaps the most likely candidate is GDF-11͞BMP-11, which is highly related to myostatin in the mature region of the protein (2,23,24) and is also expressed in skeletal muscle. Genetic studies in mice have demonstrated clear roles for Gdf11 in regulating anterior͞posterior patterning (25), kidney development (25,26), neuronal development (27,28), and pancreas development (29).…”

Section: Resultsmentioning

confidence: 99%

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

Lee

Reed

Davies

et al. 2005

Proc. Natl. Acad. Sci. U.S.A.

441

431

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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. Mice carrying a targeted mutation in the myostatin gene have muscles that are about twice the normal size as a result of a combination of muscle fiber hyperplasia and hypertrophy (2). Myostatin appears to play a similar role in other species as well; naturally occurring mutations in the myostatin gene have been shown to be responsible for the double-muscling phenotype in cattle (3-6), and recent studies have demonstrated that a human baby with approximately twice the normal muscle mass is also homozygous for a loss-of-function mutation in the MSTN gene (7). These findings have raised the possibility that agents capable of targeting the myostatin signaling pathway may be useful for increasing muscle mass for both agricultural and human therapeutic applications. In this regard, loss of myostatin signaling has been shown to have beneficial effects in mouse models of muscle degenerative (8, 9) and metabolic (10) diseases.Various myostatin-binding proteins have been identified that are capable of inhibiting myostatin activity in vitro (8,(11)(12)(13)(14)(15)(16). Two of these proteins, the JA16 neutralizing monoclonal antibody (Ab) directed against myostatin (8, 15) and a mutant form of the myostatin propeptide resistant to members of the BMP-1͞tolloid family of metalloproteases (16), have been shown to be capable of increasing muscle mass by Ϸ25% when administered to wild-type (WT) mice. To determine whether these increases in muscle growth are the maximal achievable by targeting this signaling pathway, we sought additional myostatin inhibitors that might have a broader specificity in their ability to target additional members of the TGF-␤ superfamily. Previous studies have demonstrated that myostatin is capable of binding the two activin type II receptors, ACVR2B and, to a lesser extent, ACVR2, in transfected COS cells (11,17). Moreover, transgenic mice in which a myosin light chain promoter͞ enhancer was used to express a truncated form of ACVR2B in skeletal muscle were found to have dramatic increases in muscle mass (11). Because the activin type II receptors have been shown to be capable of binding a number of other TGF-␤ family members in addition to ...

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“…Although such cleavage is sufficient for activating most TGFβ-like proteins (Hogan, 1996), prototypical family members TGFβ 1-3 remain noncovalently bound to their cleaved prodomains in latent complexes (Massague, 1998). More recently it has been demonstrated that GDF8 and 11, which share ~90% sequence identity in their mature regions (Gamer et al, 1999;Ge et al, 2005;Nakashima et al, 1999), are also noncovalently bound to their respective prodomains in latent complexes (Ge et al, 2005;Hill et al, 2002;Lee and McPherron, 2001;Wolfman et al, 2003) (Fig. 5B).…”

Section: Growth and Differentiation Factors 8 And 11 (Gdfs 8 And 11)mentioning

confidence: 99%

The bone morphogenetic protein 1/Tolloid-like metalloproteinases

2007

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A decade ago, bone morphogenetic protein 1 (BMP1) was shown to provide the activity necessary for proteolytic removal of the C-propeptides of procollagens I-III: precursors of the major fibrillar collagens. Subsequent studies have shown BMP1 to be the prototype of a small group of extracellular metalloproteinases that play manifold roles in regulating formation of the extracellular matrix (ECM). Soon after initial cloning of BMP1, genetic studies showed the related Drosophila proteinase Tolloid (TLD) to be necessary for formation of the dorsal-ventral axis in early embryogenesis. It is now clear that the BMP1/TLD-like proteinases, conserved in species ranging from Drosophila to humans, act in dorsal-ventral patterning via activation of transforming growth factor β (TGFβ)-like proteins BMP2, BMP4 (vertebrates) and decapentaplegic (arthropods). More recently, it has become apparent that the BMP1/TLD-like proteinases are key activators of a broader subset of the TGFβ superfamily of proteins, with implications that these proteinases may be key in orchestrating formation of ECM with growth factor activation and BMP signaling in morphogenetic processes.

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Expression of growth/differentiation factor 11, a new member of the BMP/TGFβ superfamily during mouse embryogenesis

Cited by 230 publications

References 9 publications

GDF11 Protects against Endothelial Injury and Reduces Atherosclerotic Lesion Formation in Apolipoprotein E-Null Mice

GDF11 Protects against Endothelial Injury and Reduces Atherosclerotic Lesion Formation in Apolipoprotein E-Null Mice

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

The bone morphogenetic protein 1/Tolloid-like metalloproteinases

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