Inhibitor-resistant type I receptors reveal specific requirements for TGF-β signaling in vivo

Ho, Diana M.; Chan, Joanne; Bayliss, Peter E.; Whitman, Malcolm

doi:10.1016/j.ydbio.2006.03.050

Cited by 48 publications

(53 citation statements)

References 41 publications

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“…The phosphorylation of Smad2 was observed to be inhibited in embryos treated with the type I receptor kinase inhibitor SB-431542 (Muèllera et al 1999;Ho et al 2006). This inhibitor did not affect the expression of HSC70.…”

Section: -1 Control Of Tgf-β β β β β Receptor Activationmentioning

confidence: 91%

Stress Protein HSP70 in Fish

Yamashita¹,

Yabu²,

Ojima³

2010

Aqua-BioSci. Monogr. (ABSM)

128

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Stress proteins (heat-shock proteins, HSPs), which comprise an evolutionally wellconserved protein family, are induced in response to a variety of stress conditions and metabolic insults. When cells are subjected to sudden environmental changes, stress proteins are induced and play a central role in cellular homeostasis. A response to sudden adverse environmental changes is referred to as the heat-shock or stress response and is accompanied by a rapid increase in the synthesis of stress proteins. Given the importance of stress proteins in thermal adaptation at the cellular level, we have studied the expression, regulation, and protective functions of the members of the HSP70 stress protein family under normal and stress conditions in a variety of fish species. HSP70/heat-shock cognate protein-70 (HSC70) plays essential roles in the receptor complex formation and activation of Activin/Nodal/transforming growth factor-β and bone morphogenetic protein receptors and facilitates Nodal signaling. In addition, chaperone-mediated autophagy assisted by HSP70/heat-shock cognate (HSC)70 may be responsible for the stress responses in fish cells. HSP70 and HSC70 translocated into the lysosomes were found to accelerate protein degradation and catabolism under both stressed and normal conditions.

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Section: -1 Control Of Tgf-β β β β β Receptor Activationmentioning

confidence: 91%

Stress Protein HSP70 in Fish

Yamashita¹,

Yabu²,

Ojima³

2010

Aqua-BioSci. Monogr. (ABSM)

128

View full text Add to dashboard Cite

show abstract

“…In amphibians, these genes are zygotically expressed under the control of the maternal T-box transcription factor Vegt (Heasman, 2006). Inhibition of Nodal signaling in Xenopus via the overexpression of Nodal antagonists or by treatment with small-molecule Nodal receptor inhibitors leads to gastrulation defects (Agius et al, 2000;Ho et al, 2006;Osada and Wright, 1999;Sun et al, 1999). Three other Smad2/3-activating TGFβs function during mesendoderm formation: Gdf1/Vg1 is maternal, while Gdf3/Derriere and Inhbb/ ActivinβB are zygotic.…”

Section: Introductionmentioning

confidence: 99%

Genome-wide view of TGFβ/Foxh1 regulation of the early mesendoderm program

et al. 2014

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Nodal/TGFβ signaling regulates diverse biological responses. By combining RNA-seq on Foxh1 and Nodal signaling loss-of-function embryos with ChIP-seq of Foxh1 and Smad2/3, we report a comprehensive genome-wide interaction between Foxh1 and Smad2/3 in mediating Nodal signaling during vertebrate mesendoderm development. This study significantly increases the total number of Nodal target genes regulated by Foxh1 and Smad2/3, and reinforces the notion that Foxh1-Smad2/3-mediated Nodal signaling directly coordinates the expression of a cohort of genes involved in the control of gene transcription, signaling pathway modulation and tissue morphogenesis during gastrulation. We also show that Foxh1 may function independently of Nodal signaling, in addition to its role as a transcription factor mediating Nodal signaling via Smad2/3. Finally, we propose an evolutionarily conserved interaction between Foxh1 and PouV, a mechanism observed in Pou5f1-mediated regulation of pluripotency in human embryonic stem and epiblast cells.

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“…We used the low molecular weight inhibitor SB431542 (Alk5/4-i), which specifically blocks TGF/Activin pathway receptors and does not affect closely related receptors from the bone morphogenetic protein (BMP) pathway or other signal transduction pathways (Ho et al, 2006;Inman et al, 2002;Jazwinska et al, 2007). The mechanism of this selectivity has recently been determined by solving the crystal structure of the mammalian TGF type I receptor kinase domain in complex with SB431542 (Ogunjimi et al, 2012).…”

mentioning

confidence: 99%

The regenerative capacity of the zebrafish heart is dependent on TGFβ signaling

2012

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SUMMARYMammals respond to a myocardial infarction by irreversible scar formation. By contrast, zebrafish are able to resolve the scar and to regenerate functional cardiac muscle. It is not known how opposing cellular responses of fibrosis and new myocardium formation are spatially and temporally coordinated during heart regeneration in zebrafish. Here, we report that the balance between the reparative and regenerative processes is achieved through Smad3-dependent TGF signaling. The type I receptor alk5b (tgfbr1b) is expressed in both fibrotic and cardiac cells of the injured heart. TGF ligands are locally induced following cryoinjury and activate the signaling pathway both in the infarct area and in cardiomyocytes in the vicinity of the trauma zone. Inhibition of the relevant type I receptors with the specific chemical inhibitor SB431542 qualitatively altered the infarct tissue and completely abolished heart regeneration. We show that transient scar formation is an essential step to maintain robustness of the damaged ventricular wall prior to cardiomyocyte replacement. Taking advantage of the reversible action of the inhibitor, we dissected the multifunctional role of TGF signaling into three crucial processes: collagen-rich scar deposition, Tenascin Cassociated tissue remodeling at the infarct-myocardium interface, and cardiomyocyte proliferation. Thus, TGF signaling orchestrates the beneficial interplay between scar-based repair and cardiomyocyte-based regeneration to achieve complete heart regeneration.

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Inhibitor-resistant type I receptors reveal specific requirements for TGF-β signaling in vivo

Cited by 48 publications

References 41 publications

Stress Protein HSP70 in Fish

Stress Protein HSP70 in Fish

Genome-wide view of TGFβ/Foxh1 regulation of the early mesendoderm program

The regenerative capacity of the zebrafish heart is dependent on TGFβ signaling

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