PMID- 10504300
OWN - NLM
STAT- MEDLINE
DCOM- 20000110
LR  - 20120625
IS  - 0021-9533 (Print)
IS  - 0021-9533 (Linking)
VI  - 112 ( Pt 20)
DP  - 1999 Oct
TI  - Characterization of bone morphogenetic protein-6 signaling pathways in osteoblast
      differentiation.
PG  - 3519-27
AB  - Bone morphogenetic protein (BMP)-6 is a member of the transforming growth factor 
      (TGF)-(&bgr;) superfamily, and is most similar to BMP-5, osteogenic protein
      (OP)-1/BMP-7, and OP-2/BMP-8. In the present study, we characterized the
      endogenous BMP-6 signaling pathway during osteoblast differentiation. BMP-6
      strongly induced alkaline phosphatase (ALP) activity in cells of osteoblast
      lineage, including C2C12 cells, MC3T3-E1 cells, and ROB-C26 cells. The profile of
      binding of BMP-6 to type I and type II receptors was similar to that of
      OP-1/BMP-7 in C2C12 cells and MC3T3-E1 cells; BMP-6 strongly bound to activin
      receptor-like kinase (ALK)-2 (also termed ActR-I), together with type II
      receptors, i.e. BMP type II receptor (BMPR-II) and activin type II receptor
      (ActR-II). In addition, BMP-6 weakly bound to BMPR-IA (ALK-3), to which BMP-2
      also bound. In contrast, binding of BMP-6 to BMPR-IB (ALK-6), and less
      efficiently to ALK-2 and BMPR-IA, together with BMPR-II was detected in ROB-C26
      cells. Intracellular signalling was further studied using C2C12 and MC3T3-E1
      cells. Among the receptor-regulated Smads activated by BMP receptors, BMP-6
      strongly induced phosphorylation and nuclear accumulation of Smad5, and less
      efficiently those of Smad1. However, Smad8 was constitutively phosphorylated, and
      no further phosphorylation or nuclear accumulation of Smad8 by BMP-6 was
      observed. These findings indicate that in the process of differentiation to
      osteoblasts, BMP-6 binds to ALK-2 as well as other type I receptors, and
      transduces signals mainly through Smad5 and possibly through Smad1.
FAU - Ebisawa, T
AU  - Ebisawa T
AD  - Department of Biochemistry, The Cancer Institute of JFCR, and Research for the
      Future Program, Japan Society for the Promotion of Science, Toshima-ku, Tokyo
      170-8455, Japan.
FAU - Tada, K
AU  - Tada K
FAU - Kitajima, I
AU  - Kitajima I
FAU - Tojo, K
AU  - Tojo K
FAU - Sampath, T K
AU  - Sampath TK
FAU - Kawabata, M
AU  - Kawabata M
FAU - Miyazono, K
AU  - Miyazono K
FAU - Imamura, T
AU  - Imamura T
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - England
TA  - J Cell Sci
JT  - Journal of cell science
JID - 0052457
RN  - 0 (Bmp6 protein, mouse)
RN  - 0 (Bone Morphogenetic Protein 6)
RN  - 0 (Bone Morphogenetic Proteins)
RN  - 0 (Receptors, Growth Factor)
RN  - 0 (Recombinant Proteins)
RN  - EC 2.7.11.1 (Protein-Serine-Threonine Kinases)
RN  - EC 2.7.11.30 (Activin Receptors, Type I)
RN  - EC 2.7.11.30 (Activin Receptors, Type II)
RN  - EC 2.7.11.30 (BMPR1A protein, human)
RN  - EC 2.7.11.30 (BMPR1B protein, human)
RN  - EC 2.7.11.30 (Bmpr2 protein, mouse)
RN  - EC 2.7.11.30 (Bone Morphogenetic Protein Receptors, Type I)
RN  - EC 2.7.11.30 (Bone Morphogenetic Protein Receptors, Type II)
RN  - EC 3.1.3.1 (Alkaline Phosphatase)
SB  - IM
MH  - 3T3 Cells
MH  - Activin Receptors, Type I
MH  - Activin Receptors, Type II
MH  - Alkaline Phosphatase/metabolism
MH  - Animals
MH  - Bone Morphogenetic Protein 6
MH  - Bone Morphogenetic Protein Receptors, Type I
MH  - Bone Morphogenetic Protein Receptors, Type II
MH  - Bone Morphogenetic Proteins/pharmacology/*physiology
MH  - Cell Differentiation
MH  - Cell Division
MH  - Cell Line
MH  - Kinetics
MH  - Mice
MH  - Osteoblasts/*cytology
MH  - Phosphorylation
MH  - Protein-Serine-Threonine Kinases/metabolism/physiology
MH  - Receptors, Growth Factor/physiology
MH  - Recombinant Proteins/metabolism
MH  - Signal Transduction/physiology
MH  - Transfection
EDAT- 1999/10/03 00:00
MHDA- 1999/10/03 00:01
CRDT- 1999/10/03 00:00
PHST- 1999/10/03 00:00 [pubmed]
PHST- 1999/10/03 00:01 [medline]
PHST- 1999/10/03 00:00 [entrez]
PST - ppublish
SO  - J Cell Sci. 1999 Oct;112 ( Pt 20):3519-27.