PMID- 20235153
OWN - NLM
STAT- MEDLINE
DCOM- 20100827
LR  - 20181113
IS  - 1097-4644 (Electronic)
IS  - 0730-2312 (Print)
IS  - 0730-2312 (Linking)
VI  - 110
IP  - 2
DP  - 2010 May 15
TI  - Connective tissue growth factor (CTGF) transactivates nuclear factor of activated 
      T-cells (NFAT) in cells of the osteoblastic lineage.
PG  - 477-83
LID - 10.1002/jcb.22561 [doi]
AB  - Connective tissue growth factor (CTGF), a member of the Cyr 61, CTGF, Nov (CCN) 
      family of proteins, regulates multiple cellular functions. Overexpression of CTGF 
      in vivo causes osteopenia, but in vitro CTGF can induce osteoblastogenesis. To 
      investigate mechanisms involved in the effects of CTGF on osteoblastic cell 
      differentiation, we examined whether CTGF modifies the activity of nuclear factor 
      of activated T-cells (NFATc) 1, a transcription factor that cooperates with 
      osterix in the formation of new bone. CTGF increased the transactivation of a 
      transiently transfected reporter construct, where 9 NFAT binding sites direct the 
      expression of luciferase (9xNFAT-Luc) and the activity of the Regulators of 
      calcineurin 1 exon 4 (Rcan1.4) promoter, an NFAT target gene. We postulated that 
      CTGF could modify the phosphorylation of NFAT by regulating glycogen synthase 
      kinase 3beta (GSK3beta). CTGF increased the mRNA levels of Protein kinase cyclic 
      guanosine monophosphate (cGMP) dependent type II (Prkg2), the gene encoding for 
      cGMP dependent protein kinase II (cGKII) which phosphorylates GSK3beta. 
      Accordingly, CTGF induced GSK3beta phosphorylation and decreased the active pool 
      of GSK3beta, a kinase that phosphorylates NFAT and leads to its nuclear export. 
      As a consequence, CTGF favored the nuclear localization of NFATc1. Downregulation 
      of PRKG2 by RNA interference reversed the effect of CTGF on the transactivation 
      of the 9xNFAT reporter construct and the Rcan 1.4 promoter, confirming the role 
      of cGKII in the activation of NFAT by CTGF. In conclusion, CTGF enhances NFAT 
      signaling through the induction of cGKII and the phosphorylation of GSK3beta.
CI  - (c) 2010 Wiley-Liss, Inc.
FAU - Smerdel-Ramoya, Anna
AU  - Smerdel-Ramoya A
AD  - Department of Research, Saint Francis Hospital and Medical Center, Hartford, 
      Connecticut, USA.
FAU - Zanotti, Stefano
AU  - Zanotti S
FAU - Canalis, Ernesto
AU  - Canalis E
LA  - eng
GR  - R01 DK045227/DK/NIDDK NIH HHS/United States
GR  - DK045227/DK/NIDDK NIH HHS/United States
GR  - R37 AR021707/AR/NIAMS NIH HHS/United States
GR  - R01 AR021707-30/AR/NIAMS NIH HHS/United States
GR  - AR021707/AR/NIAMS NIH HHS/United States
GR  - R01 AR021707/AR/NIAMS NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PL  - United States
TA  - J Cell Biochem
JT  - Journal of cellular biochemistry
JID - 8205768
RN  - 0 (DNA Primers)
RN  - 0 (NFATC Transcription Factors)
RN  - 0 (Nfatc1 protein, mouse)
RN  - 139568-91-5 (Connective Tissue Growth Factor)
RN  - EC 2.7.11.1 (Glycogen Synthase Kinase 3 beta)
RN  - EC 2.7.11.1 (Gsk3b protein, mouse)
RN  - EC 2.7.11.26 (Glycogen Synthase Kinase 3)
SB  - IM
MH  - Animals
MH  - Base Sequence
MH  - Blotting, Western
MH  - Cell Line
MH  - Connective Tissue Growth Factor/*physiology
MH  - DNA Primers
MH  - Glycogen Synthase Kinase 3/metabolism
MH  - Glycogen Synthase Kinase 3 beta
MH  - Mice
MH  - NFATC Transcription Factors/*genetics
MH  - Osteoblasts/*metabolism
MH  - RNA Interference
MH  - Reverse Transcriptase Polymerase Chain Reaction
MH  - Transcriptional Activation/*physiology
PMC - PMC3008370
MID - NIHMS257410
EDAT- 2010/03/18 06:00
MHDA- 2010/08/28 06:00
PMCR- 2011/05/15
CRDT- 2010/03/18 06:00
PHST- 2010/03/18 06:00 [entrez]
PHST- 2010/03/18 06:00 [pubmed]
PHST- 2010/08/28 06:00 [medline]
PHST- 2011/05/15 00:00 [pmc-release]
AID - 10.1002/jcb.22561 [doi]
PST - ppublish
SO  - J Cell Biochem. 2010 May 15;110(2):477-83. doi: 10.1002/jcb.22561.