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Protein associated with SMAD1 (PAWS1/FAM83G) is a substrate for type I bone morphogenetic protein receptors and modulates bone morphogenetic protein signalling

Bone morphogenetic proteins (BMPs) control multiple cellular processes in embryos and adult tissues. BMPs signal through the activation of type I BMP receptor kinases, which then phosphorylate SMADs 1/5/8. In the canonical pathway, this triggers the association of these SMADs with SMAD4 and their tr...

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Autores principales: Vogt, Janis, Dingwell, Kevin S., Herhaus, Lina, Gourlay, Robert, Macartney, Thomas, Campbell, David, Smith, James C., Sapkota, Gopal P.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: The Royal Society 2014
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3938053/
https://www.ncbi.nlm.nih.gov/pubmed/24554596
http://dx.doi.org/10.1098/rsob.130210
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author Vogt, Janis
Dingwell, Kevin S.
Herhaus, Lina
Gourlay, Robert
Macartney, Thomas
Campbell, David
Smith, James C.
Sapkota, Gopal P.
author_facet Vogt, Janis
Dingwell, Kevin S.
Herhaus, Lina
Gourlay, Robert
Macartney, Thomas
Campbell, David
Smith, James C.
Sapkota, Gopal P.
author_sort Vogt, Janis
collection PubMed
description Bone morphogenetic proteins (BMPs) control multiple cellular processes in embryos and adult tissues. BMPs signal through the activation of type I BMP receptor kinases, which then phosphorylate SMADs 1/5/8. In the canonical pathway, this triggers the association of these SMADs with SMAD4 and their translocation to the nucleus, where they regulate gene expression. BMPs can also signal independently of SMAD4, but this pathway is poorly understood. Here, we report the discovery and characterization of PAWS1/FAM83G as a novel SMAD1 interactor. PAWS1 forms a complex with SMAD1 in a SMAD4-independent manner, and BMP signalling induces the phosphorylation of PAWS1 through BMPR1A. The phosphorylation of PAWS1 in response to BMP is essential for activation of the SMAD4-independent BMP target genes NEDD9 and ASNS. Our findings identify PAWS1 as the first non-SMAD substrate for type I BMP receptor kinases and as a novel player in the BMP pathway. We also demonstrate that PAWS1 regulates the expression of several non-BMP target genes, suggesting roles for PAWS1 beyond the BMP pathway.
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spelling pubmed-39380532014-03-12 Protein associated with SMAD1 (PAWS1/FAM83G) is a substrate for type I bone morphogenetic protein receptors and modulates bone morphogenetic protein signalling Vogt, Janis Dingwell, Kevin S. Herhaus, Lina Gourlay, Robert Macartney, Thomas Campbell, David Smith, James C. Sapkota, Gopal P. Open Biol Research Bone morphogenetic proteins (BMPs) control multiple cellular processes in embryos and adult tissues. BMPs signal through the activation of type I BMP receptor kinases, which then phosphorylate SMADs 1/5/8. In the canonical pathway, this triggers the association of these SMADs with SMAD4 and their translocation to the nucleus, where they regulate gene expression. BMPs can also signal independently of SMAD4, but this pathway is poorly understood. Here, we report the discovery and characterization of PAWS1/FAM83G as a novel SMAD1 interactor. PAWS1 forms a complex with SMAD1 in a SMAD4-independent manner, and BMP signalling induces the phosphorylation of PAWS1 through BMPR1A. The phosphorylation of PAWS1 in response to BMP is essential for activation of the SMAD4-independent BMP target genes NEDD9 and ASNS. Our findings identify PAWS1 as the first non-SMAD substrate for type I BMP receptor kinases and as a novel player in the BMP pathway. We also demonstrate that PAWS1 regulates the expression of several non-BMP target genes, suggesting roles for PAWS1 beyond the BMP pathway. The Royal Society 2014-02-19 /pmc/articles/PMC3938053/ /pubmed/24554596 http://dx.doi.org/10.1098/rsob.130210 Text en http://creativecommons.org/licenses/by/3.0/ © 2014 The Authors. Published by the Royal Society under the terms of the Creative Commons Attribution License http://creativecommons.org/licenses/by/3.0/, which permits unrestricted use, provided the original author and source are credited.
spellingShingle Research
Vogt, Janis
Dingwell, Kevin S.
Herhaus, Lina
Gourlay, Robert
Macartney, Thomas
Campbell, David
Smith, James C.
Sapkota, Gopal P.
Protein associated with SMAD1 (PAWS1/FAM83G) is a substrate for type I bone morphogenetic protein receptors and modulates bone morphogenetic protein signalling
title Protein associated with SMAD1 (PAWS1/FAM83G) is a substrate for type I bone morphogenetic protein receptors and modulates bone morphogenetic protein signalling
title_full Protein associated with SMAD1 (PAWS1/FAM83G) is a substrate for type I bone morphogenetic protein receptors and modulates bone morphogenetic protein signalling
title_fullStr Protein associated with SMAD1 (PAWS1/FAM83G) is a substrate for type I bone morphogenetic protein receptors and modulates bone morphogenetic protein signalling
title_full_unstemmed Protein associated with SMAD1 (PAWS1/FAM83G) is a substrate for type I bone morphogenetic protein receptors and modulates bone morphogenetic protein signalling
title_short Protein associated with SMAD1 (PAWS1/FAM83G) is a substrate for type I bone morphogenetic protein receptors and modulates bone morphogenetic protein signalling
title_sort protein associated with smad1 (paws1/fam83g) is a substrate for type i bone morphogenetic protein receptors and modulates bone morphogenetic protein signalling
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3938053/
https://www.ncbi.nlm.nih.gov/pubmed/24554596
http://dx.doi.org/10.1098/rsob.130210
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