PMID- 18403485
OWN - NLM
STAT- MEDLINE
DCOM- 20080922
LR  - 20131121
IS  - 0013-7227 (Print)
IS  - 0013-7227 (Linking)
VI  - 149
IP  - 7
DP  - 2008 Jul
TI  - Distinct modes of activation of phosphatidylinositol 3-kinase in response to 
      cyclic adenosine 3', 5'-monophosphate or insulin-like growth factor I play 
      different roles in regulation of cyclin D1 and p27Kip1 in FRTL-5 cells.
PG  - 3729-42
LID - 10.1210/en.2007-1443 [doi]
AB  - Bioactivities of IGFs in various cells are often potentiated in the presence of 
      other hormones. In previous studies we showed that pretreatment of rat FRTL-5 
      thyroid cells with TSH or other cAMP-generating agents markedly potentiated DNA 
      synthesis induced by IGF-I. Under these conditions we found that 
      phosphatidylinositol (PI) 3-kinase was activated in response to either cAMP or 
      IGF stimulus, and both activation modes were indispensable for the potentiation 
      of DNA synthesis. The present studies were undertaken to elucidate how cAMP 
      and/or IGF-I stimulus regulated the G1 cyclin-cyclin dependent kinase 
      (CDK)-inhibitor system, and to determine the roles of PI 3-kinase activation by 
      cAMP or IGF-I stimulus in this system. We found that cAMP pretreatment enhanced 
      IGF-I-dependent increases in cyclin D1, due to synergistic increases in mRNA and 
      elevation of translation rates. Furthermore, cAMP pretreatment enhanced 
      IGF-I-induced protein degradation of the CDK inhibitor, p27(Kip1). These changes 
      well explained an increase in cyclin E, leading to marked activation of G1 CDKs, 
      followed by retinoblastoma protein phosphorylation. Our results using a PI 
      3-kinase inhibitor showed that cAMP-dependent PI 3-kinase activation plays an 
      important role in the increase in cyclin D1 translation. In contrast, 
      IGF-I-dependent PI 3-kinase activation was required for the increase in cyclin D1 
      mRNA levels and degradation of p27(Kip1). Together, the present study elucidates 
      the role of cAMP and IGF-I in differentially activating PI 3-kinase as a mediator 
      of multiple molecular events. These events converge in the regulation of cyclin 
      D1 and p27(Kip1), leading to cAMP-dependent potentiation of IGF-I-dependent CDK 
      activation and DNA synthesis.
FAU - Fukushima, Toshiaki
AU  - Fukushima T
AD  - Laboratory of Cell Regulation, Departments of Animal Sciences and Applied 
      Biological Chemistry, Graduate School of Agriculture and Life Sciences, The 
      University of Tokyo, 1-1-1 Yayoi, Bunkyo-ku, Tokyo, Japan.
FAU - Nedachi, Taku
AU  - Nedachi T
FAU - Akizawa, Hidenori
AU  - Akizawa H
FAU - Akahori, Masakazu
AU  - Akahori M
FAU - Hakuno, Fumihiko
AU  - Hakuno F
FAU - Takahashi, Shin-Ichiro
AU  - Takahashi S
LA  - eng
PT  - Journal Article
DEP - 20080410
PL  - United States
TA  - Endocrinology
JT  - Endocrinology
JID - 0375040
RN  - 0 (RNA, Messenger)
RN  - 136601-57-5 (Cyclin D1)
RN  - 147604-94-2 (Cyclin-Dependent Kinase Inhibitor p27)
RN  - 67763-96-6 (Insulin-Like Growth Factor I)
RN  - E0399OZS9N (Cyclic AMP)
RN  - EC 2.7.1.- (Phosphatidylinositol 3-Kinases)
RN  - EC 2.7.11.22 (Cyclin-Dependent Kinases)
SB  - IM
MH  - Animals
MH  - Blotting, Northern
MH  - Cell Cycle/drug effects
MH  - Cell Line
MH  - Cyclic AMP/*pharmacology
MH  - Cyclin D1/genetics/*metabolism
MH  - Cyclin-Dependent Kinase Inhibitor p27/*metabolism
MH  - Cyclin-Dependent Kinases/metabolism
MH  - DNA Replication/drug effects
MH  - Enzyme Activation/drug effects
MH  - Gene Expression Regulation/drug effects
MH  - Immunoblotting
MH  - Immunoprecipitation
MH  - Insulin-Like Growth Factor I/*pharmacology
MH  - Phosphatidylinositol 3-Kinases/*metabolism
MH  - RNA, Messenger/genetics/metabolism
MH  - Rats
EDAT- 2008/04/12 09:00
MHDA- 2008/09/23 09:00
CRDT- 2008/04/12 09:00
PHST- 2008/04/12 09:00 [pubmed]
PHST- 2008/09/23 09:00 [medline]
PHST- 2008/04/12 09:00 [entrez]
AID - en.2007-1443 [pii]
AID - 10.1210/en.2007-1443 [doi]
PST - ppublish
SO  - Endocrinology. 2008 Jul;149(7):3729-42. doi: 10.1210/en.2007-1443. Epub 2008 Apr 
      10.