GONUTS has been updated to MW1.31 Most things seem to be working but be sure to report problems.

Have any questions? Please email us at ecoliwiki@gmail.com

PMID:15766759

From GONUTS
Jump to: navigation, search
Citation

Desgrosellier, JS, Mundell, NA, McDonnell, MA, Moses, HL and Barnett, JV (2005) Activin receptor-like kinase 2 and Smad6 regulate epithelial-mesenchymal transformation during cardiac valve formation. Dev. Biol. 280:201-10

Abstract

Epithelial-mesenchymal transformation (EMT) occurs during both development and tumorigenesis. Transforming growth factor beta (TGFbeta) ligands signal EMT in the atrioventricular (AV) cushion of the developing heart, a critical step in valve formation. TGFbeta signals through a complex of type I and type II receptors. Several type I receptors exist although activin receptor-like kinase (ALK) 5 mediates the majority of TGFbeta signaling. Here, we demonstrate that ALK2 is sufficient to induce EMT in the heart. Both ALK2 and ALK5 are expressed throughout the heart with ALK2 expressed abundantly in endocardial cells of the outflow tract (OFT), ventricle, and AV cushion. Misexpression of constitutively active (ca) ALK2 in non-transforming ventricular endocardial cells induced EMT, while caALK5 did not, thus demonstrating that ALK2 activity alone is sufficient to stimulate EMT. Smad6, an inhibitor of Smad signaling downstream of ALK2, but not ALK5, inhibited EMT in AV cushion endocardial cells. These data suggest that ALK2 activation may stimulate EMT in the AV cushion and that Smad6 may act downstream of ALK2 to negatively regulate EMT.

Links

PubMed Online version:10.1016/j.ydbio.2004.12.037

Keywords

Activin Receptors, Type I/genetics; Activin Receptors, Type I/metabolism; Activin Receptors, Type II/genetics; Activin Receptors, Type II/metabolism; Adenoviridae/genetics; Adenoviridae/metabolism; Alkaline Phosphatase/metabolism; Animals; Chick Embryo; DNA-Binding Proteins/metabolism; Endocardium/metabolism; Epithelium/physiology; Gene Transfer Techniques; Green Fluorescent Proteins/genetics; Green Fluorescent Proteins/metabolism; Heart Valves/cytology; Heart Valves/embryology; In Situ Hybridization; Mesoderm/physiology; Morphogenesis/physiology; Protein-Serine-Threonine Kinases; Receptors, Transforming Growth Factor beta/genetics; Receptors, Transforming Growth Factor beta/metabolism; Signal Transduction/physiology; Smad6 Protein; Trans-Activators/metabolism; Transforming Growth Factor beta/metabolism

Significance

Annotations

Gene product Qualifier GO Term Evidence Code with/from Aspect Extension Notes Status

CHICK:ACVR1

involved_in

GO:0010694: positive regulation of alkaline phosphatase activity

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete

CHICK:ACVR1

involved_in

GO:0010718: positive regulation of epithelial to mesenchymal transition

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete

CHICK:ACVR1

involved_in

GO:0042118: endothelial cell activation

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete

CHICK:ACVR1

involved_in

GO:0060317: cardiac epithelial to mesenchymal transition

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete

CHICK:ACVR1

involved_in

GO:0045893: positive regulation of transcription, DNA-templated

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete

CHICK:Q06900

involved_in

GO:0045893: positive regulation of transcription, DNA-templated

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete

CHICK:Q06900

NOT|involved_in

GO:0010692: regulation of alkaline phosphatase activity

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete


See also

References

See Help:References for how to manage references in GONUTS.