Growth differentiation factor 11 signals through the transforming growth factor‐β receptor ALK5 to regionalize the anterior–posterior axis

Andersson, Olov; Reissmann, Eva; Ibáñez, Carlos F.

doi:10.1038/sj.embor.7400752

Cited by 143 publications

(144 citation statements)

References 20 publications

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“…The absence of tail and presence of extra thoracic and lumbar segments in cKO embryos were also observed in embryos deficient in Gdf11 (19) or its main downstream receptors, activin type IIB (23) and ALK5 (24). Gdf11 is a secreted member of the TGF␤ superfamily that participates in the establishment of the anterior-posterior axis by controlling the spatiotemporal expression of Hox genes.…”

Section: Discussionmentioning

confidence: 98%

In vivo functions of the proprotein convertase PC5/6 during mouse development: Gdf11 is a likely substrate

Essalmani

Zaid

Marcinkiewicz

et al. 2008

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

114

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The proprotein convertase PC5/6 cleaves protein precursors after basic amino acids and is essential for implantation in CD1/129/Sv/ C57BL/6 mixed-background mice. Conditional inactivation of Pcsk5 in the epiblast but not in the extraembryonic tissue bypassed early embryonic lethality but resulted in death at birth. PC5/6-deficient embryos exhibited Gdf11-related phenotypes such as altered anteroposterior patterning with extra vertebrae and lack of tail and kidney agenesis. They also exhibited Gdf11-independent phenotypes, such as a smaller size, multiple hemorrhages, collapsed alveoli, and retarded ossification. In situ hybridization revealed overlapping PC5/6 and Gdf11 mRNA expression patterns. In vitro and ex vivo analyses showed that the selectivity of PC5/6 for Gdf11 essentially resides in the presence of a P1 Asn in the RSRR2N cleavage motif. This work identifies Gdf11 as a likely in vivo specific substrate of PC5/6 and opens the way to the identification of other key substrates of this convertase.Furin-like ͉ Meox2-cre ͉ Pcsk5

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Section: Discussionmentioning

confidence: 98%

In vivo functions of the proprotein convertase PC5/6 during mouse development: Gdf11 is a likely substrate

Essalmani

Zaid

Marcinkiewicz

et al. 2008

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

114

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show abstract

“…ES reduced expression of Smad3, a transcriptional regulator that is a downstream effector of receptors for activins, myostatin, and GDF11 (55). Smad3 is important for RANKL-induced osteoclastogenic signaling, and activins have been reported to reduce bone mass in adulthood (56).…”

Section: Effects Of Sci-and Es-induced Muscle Contraction On Other Simentioning

confidence: 99%

The Central Nervous System (CNS)-independent Anti-bone-resorptive Activity of Muscle Contraction and the Underlying Molecular and Cellular Signatures

Qin

Sun

Cao

et al. 2013

Journal of Biological Chemistry

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Background: Mechanisms by which muscle regulates bone are poorly understood. Results: Electrically stimulated muscle contraction reversed elevations in bone resorption and increased Wnt signaling in bone-derived cells after spinal cord transection. Conclusion: Muscle contraction reduced resorption of unloaded bone independently of the CNS, through mechanical effects and, potentially, nonmechanical signals (e.g. myokines). Significance: The study provides new insights regarding muscle-bone interactions.

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“…ALK2 (ACVR1) was termed an activin type I receptor since it could bind activins; however, it is highly likely that ALK2 acts as a type I receptor for BMPs [15]. Myostatin and GDF11 bind ActRIIB and ActRIIA and utilize ALK5 and ALK4 as type I receptors [24][25][26] ( Table 1).…”

Section: Activin Receptors and Their Unique Signal Transduction Pmentioning

confidence: 99%

Signal Transduction Pathway through Activin Receptors as a Therapeutic Target of Musculoskeletal Diseases and Cancer

et al. 2008

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Abstract. Activin, myostatin and other members of the TGF-β superfamily signal through a combination of type II and type I receptors, both of which are transmembrane serine/threonine kinases. Activin type II receptors, ActRIIA and ActRIIB, are primary ligand binding receptors for activins, nodal, myostatin and GDF11. ActRIIs also bind a subset of bone morphogenetic proteins (BMPs). Type I receptors that form complexes with ActRIIs are dependent on ligands. In the case of activins and nodal, activin receptor-like kinases 4 and 7 (ALK4 and ALK7) are the authentic type I receptors. Myostatin and GDF11 utilize ALK5, although ALK4 could also be activated by these growth factors. ALK4, 5 and 7 are structurally and functionally similar and activate receptor-regulated Smads for TGF-β, Smad2 and 3. BMPs signal through a combination of three type II receptors, BMPRII, ActRIIA, and ActRIIB and four type I receptors, ALK1, 2, 3, and 6. BMPs activate BMP-specific Smads, Smad1, 5 and 8. Smad proteins undergo multimerization with co-mediator Smad, Smad4, and translocated into the nucleus to regulate the transcription of target genes in cooperation with nuclear cofactors. The signal transduction pathway through activin type II receptors, ActRIIA and ActRIIB, with type I receptors is involved in various human diseases. In this review, we discuss the role of signaling through activin receptors as therapeutic targets of intractable neuromuscular diseases, endocrine disorders and cancers.

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Growth differentiation factor 11 signals through the transforming growth factor‐β receptor ALK5 to regionalize the anterior–posterior axis

Cited by 143 publications

References 20 publications

In vivo functions of the proprotein convertase PC5/6 during mouse development: Gdf11 is a likely substrate

In vivo functions of the proprotein convertase PC5/6 during mouse development: Gdf11 is a likely substrate

The Central Nervous System (CNS)-independent Anti-bone-resorptive Activity of Muscle Contraction and the Underlying Molecular and Cellular Signatures

Signal Transduction Pathway through Activin Receptors as a Therapeutic Target of Musculoskeletal Diseases and Cancer

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