The TGF-β family mediator Smad1 is phosphorylated directly and activated functionally by the BMP receptor kinase Journal Article

  

Authors:	Kretzschmar, M.; Liu, F.; Hata, A.; Doody, J.; Massagué, J.
Article Title:	The TGF-β family mediator Smad1 is phosphorylated directly and activated functionally by the BMP receptor kinase
Abstract:	Bone morphogenetic proteins (BMPs) are members of the TGF-β family that regulate cell proliferation, apoptosis, and differentiation, and participate in the development of most tissues and organs in vertebrates. Smad proteins function downstream of TGF-β receptor serine/threonine kinases and undergo serine phosphorylation in response to receptor activation. Smad1 is regulated in this fashion by BMP receptors, and Smad2 and Smad3 by TGF-β and activin receptors. Here, we report that BMP receptors phosphorylate and activate Smad1 directly. Phosphorylation of Smad1 in vivo involves serines in the carboxy-terminal motif SSXS. These residues are phosphorylated directly by a BMP type I receptor in vitro. Mutation of these carboxy-terminal serines prevents several Smad1 activation events, namely, Smad1 association with the related protein DPC4, accumulation in the nucleus, and gain of transcriptional activity. Similar carboxy-terminal serines in Smad2 are required for its phosphorylation and association with DPC4 in response to TGF-β, indicating the generality of this process of Smad activation. As a direct physiological substrate of BMP receptors, Smad1 provides a link between receptor serine/threonine kinases and the nucleus.
Keywords:	signal transduction; protein phosphorylation; mutation; dna-binding proteins; nonhuman; animal cell; animals; bone morphogenetic protein; serine; smad2 protein; transforming growth factor beta; carboxy terminal sequence; cell line; protein binding; genetic transcription; enzyme substrate; protein serine threonine kinase; cos cells; phosphorylation; animalia; vertebrata; amino acid sequence; molecular sequence data; protein-serine-threonine kinases; lung; smad proteins; epithelial cells; trans-activators; cell nucleus; receptor; mink; receptors, growth factor; phosphopeptides; bmp; antigen antibody complex; cell receptor; tgf-β; bone morphogenetic protein receptors, type i; dpc4; activin receptors, type i; priority journal; article; bone morphogenetic protein receptors, type ii; smad1; activin receptors
Journal Title:	Genes and Development
Volume:	11
Issue:	8
ISSN:	0890-9369
Publisher:	Cold Spring Harbor Laboratory Press
Date Published:	1997-04-15
Start Page:	984
End Page:	995
Language:	English
PUBMED:	9136927
PROVIDER:	scopus
DOI:	10.1101/gad.11.8.984
DOI/URL:	https://www.scopus.com/inward/record.uri?eid=2-s2.0-0030911104&partnerID=40&md5=00d4d010e676f23a7a1419266301da56
Notes:	Article -- Export Date: 17 March 2017 -- Source: Scopus

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