PMID- 12647306
OWN - NLM
STAT- MEDLINE
DCOM- 20031211
LR  - 20211203
IS  - 0730-2312 (Print)
IS  - 0730-2312 (Linking)
VI  - 88
IP  - 6
DP  - 2003 Apr 15
TI  - Inhibition of phosphatidylinositol 3-kinase and p70S6 kinase blocks osteogenic 
      protein-1 induction of alkaline phosphatase activity in fetal rat calvaria cells.
PG  - 1247-55
AB  - Published studies reveal that Osteogenic Protein-1 (OP-1) and insulin-like growth 
      factor-I (IGF-I) synergistically stimulate alkaline phosphatase (AP) activity and 
      bone nodule formation in fetal rat calvaria (FRC) cells. In the present study, we 
      examined whether there are interactions between the signal transduction pathways 
      activated by these two growth factors. OP-1 did not significantly affect the 
      levels of IRS-1, IRS-2, the p85alpha subunit of phosphatidylinositol 3-kinase (PI 
      3-kinase) or the extracellular signal-regulated kinase (ERK)-2, but stimulated 
      ERK-1 protein by twofold. OP-1 also induced phosphorylation of ERK-1 and -2, but 
      not of Akt/protein kinase B (PKB), a protein kinase that is downstream of PI 
      3-kinase. By comparison, IGF-I increased the levels of the phosphorylated forms 
      of ERK-1 and -2, and Akt/PKB. Inhibition of ERK activation by PD98059 did not 
      significantly alter the stimulation of AP activity by OP-1 or OP-1 in combination 
      with IGF-I. In contrast, inhibition of PI 3-kinase activity by LY294002 blocked 
      the induction of AP activity by OP-1 and OP-1 plus IGF-I. Treatment of cells with 
      rapamycin, an inhibitor of the mammalian target of mTOR, resulted in a 47% and a 
      53% decrease in the AP activity induced by OP-1 alone and by OP-1 plus IGF-I, 
      respectively. These studies suggest that PI 3-kinase and mTOR contribute to the 
      induction of AP activity by OP-1 and the synergistic effect of OP-1 and IGF-I on 
      AP activity in FRC cells.
CI  - Copyright 2003 Wiley-Liss, Inc.
FAU - Shoba, Lungile N N
AU  - Shoba LN
AD  - Department of Biochemistry, University of Texas Health Science Center at San 
      Antonio, 7703 Floyd Curl Drive, San Antonio, Texas 78229-3900, USA.
FAU - Lee, John C
AU  - Lee JC
LA  - eng
PT  - Journal Article
PL  - United States
TA  - J Cell Biochem
JT  - Journal of cellular biochemistry
JID - 8205768
RN  - 0 (Bmp7 protein, rat)
RN  - 0 (Bone Morphogenetic Protein 7)
RN  - 0 (Bone Morphogenetic Proteins)
RN  - 0 (Chromones)
RN  - 0 (Enzyme Inhibitors)
RN  - 0 (Flavonoids)
RN  - 0 (Morpholines)
RN  - 0 (Phosphoinositide-3 Kinase Inhibitors)
RN  - 0 (Proto-Oncogene Proteins)
RN  - 0 (Transforming Growth Factor beta)
RN  - 31M2U1DVID (2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one)
RN  - 67763-96-6 (Insulin-Like Growth Factor I)
RN  - EC 2.7.11.1 (Akt1 protein, rat)
RN  - EC 2.7.11.1 (Protein Serine-Threonine Kinases)
RN  - EC 2.7.11.1 (Proto-Oncogene Proteins c-akt)
RN  - EC 2.7.11.1 (Ribosomal Protein S6 Kinases, 70-kDa)
RN  - EC 3.1.3.1 (Alkaline Phosphatase)
RN  - SJE1IO5E3I (2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one)
RN  - W36ZG6FT64 (Sirolimus)
SB  - IM
MH  - Alkaline Phosphatase/analysis/biosynthesis/*metabolism
MH  - Animals
MH  - Bone Morphogenetic Protein 7
MH  - Bone Morphogenetic Proteins/pharmacology/*physiology
MH  - Cell Differentiation/drug effects
MH  - Cells, Cultured
MH  - Chromones/pharmacology
MH  - Enzyme Induction/drug effects
MH  - Enzyme Inhibitors/pharmacology
MH  - Fetus
MH  - Flavonoids/pharmacology
MH  - Insulin-Like Growth Factor I/biosynthesis/pharmacology
MH  - Morpholines/pharmacology
MH  - *Phosphoinositide-3 Kinase Inhibitors
MH  - Phosphorylation
MH  - *Protein Serine-Threonine Kinases
MH  - Proto-Oncogene Proteins/metabolism
MH  - Proto-Oncogene Proteins c-akt
MH  - Rats
MH  - Ribosomal Protein S6 Kinases, 70-kDa/*antagonists & inhibitors
MH  - *Signal Transduction/drug effects
MH  - Sirolimus/pharmacology
MH  - Skull/*drug effects/embryology
MH  - *Transforming Growth Factor beta
EDAT- 2003/03/21 04:00
MHDA- 2003/12/12 05:00
CRDT- 2003/03/21 04:00
PHST- 2003/03/21 04:00 [pubmed]
PHST- 2003/12/12 05:00 [medline]
PHST- 2003/03/21 04:00 [entrez]
AID - 10.1002/jcb.10474 [doi]
PST - ppublish
SO  - J Cell Biochem. 2003 Apr 15;88(6):1247-55. doi: 10.1002/jcb.10474.