Differential inhibition of Smad6 and Smad7 on bone morphogenetic protein- and activin-mediated growth arrest and apoptosis in B cells

A Ishisaki; K Yamato; S Hashimoto; A Nakao; K Tamaki; K Nonaka; P ten Dijke; H Sugino; T Nishihara

doi:10.1074/jbc.274.19.13637

Differential inhibition of Smad6 and Smad7 on bone morphogenetic protein- and activin-mediated growth arrest and apoptosis in B cells

J Biol Chem. 1999 May 7;274(19):13637-42. doi: 10.1074/jbc.274.19.13637.

Authors

A Ishisaki¹, K Yamato, S Hashimoto, A Nakao, K Tamaki, K Nonaka, P ten Dijke, H Sugino, T Nishihara

Affiliation

¹ Department of Oral Science, National Institute of Infectious Diseases, 1-23-1 Toyama, Shinjuku-ku, Tokyo 162-8640, Japan.

PMID: 10224135
DOI: 10.1074/jbc.274.19.13637

Abstract

Smad6 and Smad7 prevent ligand-induced activation of signal-transducing Smad proteins in the transforming growth factor-beta family. Here we demonstrate that both Smad6 and Smad7 are human bone morphogenetic protein-2 (hBMP-2)-inducible antagonists of hBMP-2-induced growth arrest and apoptosis in mouse B cell hybridoma HS-72 cells. Moreover, we confirmed that the ectopic expressions of Smad6 and Smad7 inhibited the hBMP-2-induced Smad1/Smad5 phosphorylation. We previously reported that Smad7 is an activin A-inducible antagonist of activin A-induced growth arrest and apoptosis in HS-72 cells. Interestingly, although mRNA expression of Smad6 was induced by activin A in HS-72 cells, Smad6 showed no antagonistic effect on activin A-induced growth arrest and apoptosis. Moreover, we found that the ectopic expression of Smad7, but not Smad6, inhibited the activin A-induced Smad2 phosphorylation in HS-72 cells. Thus, Smad6 and Smad7 exhibit differential inhibitory effects in bone morphogenetic protein-2- and activin A-mediated signaling in B lineage cells.

Publication types

Comparative Study
Research Support, Non-U.S. Gov't

MeSH terms

Activins
Animals
Apoptosis
B-Lymphocytes / cytology*
Bone Morphogenetic Protein 2
Bone Morphogenetic Proteins / antagonists & inhibitors*
Bone Morphogenetic Proteins / physiology
Cell Division
Cell Line
Cyclin-Dependent Kinase Inhibitor p21
Cyclins / metabolism
DNA-Binding Proteins / genetics
DNA-Binding Proteins / metabolism*
Humans
Inhibins / antagonists & inhibitors*
Inhibins / physiology
Mice
Phosphorylation
RNA, Messenger / genetics
RNA, Messenger / metabolism
Smad6 Protein
Smad7 Protein
Trans-Activators / genetics
Trans-Activators / metabolism*
Transforming Growth Factor beta*

Substances

BMP2 protein, human
Bmp2 protein, mouse
Bone Morphogenetic Protein 2
Bone Morphogenetic Proteins
CDKN1A protein, human
Cdkn1a protein, mouse
Cyclin-Dependent Kinase Inhibitor p21
Cyclins
DNA-Binding Proteins
RNA, Messenger
SMAD6 protein, human
SMAD7 protein, human
Smad6 Protein
Smad6 protein, mouse
Smad7 Protein
Smad7 protein, mouse
Trans-Activators
Transforming Growth Factor beta
Activins
Inhibins