PMID- 17893321
OWN - NLM
STAT- MEDLINE
DCOM- 20071213
LR  - 20181113
IS  - 1098-5549 (Electronic)
IS  - 0270-7306 (Print)
IS  - 0270-7306 (Linking)
VI  - 27
IP  - 23
DP  - 2007 Dec
TI  - Serum withdrawal-induced accumulation of phosphoinositide 3-kinase lipids in 
      differentiating 3T3-L6 myoblasts: distinct roles for Ship2 and PTEN.
PG  - 8098-112
AB  - Phosphoinositide 3-kinase (PI3K) activation and synthesis of 
      phosphatidylinositol-3,4-bisphosphate (PI-3,4-P2) and 
      phosphatidylinositol-3,4,5-trisphosphate (PI-3,4,5-P3) lipids mediate growth 
      factor signaling that leads to cell proliferation, migration, and survival. 
      PI3K-dependent activation of Akt is critical for myoblast differentiation induced 
      by serum withdrawal, suggesting that in these cells PI3K signaling is activated 
      in an unconventional manner. Here we investigate the mechanisms by which PI3K 
      signaling and Akt are regulated during myogenesis. We report that PI-3,4-P2 and 
      PI-3,4,5-P3 accumulated in the plasma membranes of serum-starved 3T3-L6 myoblasts 
      due to de novo synthesis and increased lipid stability. Surprisingly, only newly 
      synthesized lipids were capable of activating Akt. Knockdown of the lipid 
      phosphatase PTEN moderately increased PI3K lipids but significantly increased Akt 
      phosphorylation and promoted myoblast differentiation. Knockdown of the lipid 
      phosphatase Ship2, on the other hand, dramatically increased the steady-state 
      levels of PI-3,4,5-P3 but did not affect Akt phosphorylation and increased 
      apoptotic cell death. Together, these results reveal the existence of two 
      distinct pools of PI3K lipids in differentiating 3T3-L6 myoblasts: a pool of 
      nascent lipids that is mainly dephosphorylated by PTEN and is capable of 
      activating Akt and promoting myoblast differentiation and a stable pool that is 
      dephosphorylated by Ship2 and is unable to activate Akt.
FAU - Mandl, Adel
AU  - Mandl A
AD  - Boston Biomedical Research Institute, 64 Grove Street, Watertown, MA 02472, USA.
FAU - Sarkes, Deborah
AU  - Sarkes D
FAU - Carricaburu, Valerie
AU  - Carricaburu V
FAU - Jung, Vanessa
AU  - Jung V
FAU - Rameh, Lucia
AU  - Rameh L
LA  - eng
GR  - NIDDK 63219/PHS HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
DEP - 20070924
PL  - United States
TA  - Mol Cell Biol
JT  - Molecular and cellular biology
JID - 8109087
RN  - 0 (Insulin)
RN  - 0 (Mutant Proteins)
RN  - 0 (Phosphatidylinositol 4,5-Diphosphate)
RN  - 0 (Phosphatidylinositol Phosphates)
RN  - 0 (phosphatidylinositol 3,4,5-triphosphate)
RN  - EC 2.7.1.- (Phosphatidylinositol 3-Kinases)
RN  - EC 2.7.11.1 (Proto-Oncogene Proteins c-akt)
RN  - EC 3.1.3.2 (Phosphoric Monoester Hydrolases)
RN  - EC 3.1.3.56 (Inositol Polyphosphate 5-Phosphatases)
RN  - EC 3.1.3.67 (PTEN Phosphohydrolase)
RN  - EC 3.1.3.67 (Pten protein, rat)
RN  - EC 3.1.3.86 (Inppl1 protein, mouse)
RN  - EC 3.1.3.86 (Inppl1 protein, rat)
RN  - EC 3.1.3.86 (Phosphatidylinositol-3,4,5-Trisphosphate 5-Phosphatases)
SB  - IM
MH  - Animals
MH  - Catalysis/drug effects
MH  - *Cell Differentiation/drug effects
MH  - Cell Proliferation/drug effects
MH  - Cell Survival/drug effects
MH  - HeLa Cells
MH  - Humans
MH  - Inositol Polyphosphate 5-Phosphatases
MH  - Insulin/pharmacology
MH  - Mice
MH  - Mutant Proteins/metabolism
MH  - Myoblasts/cytology/drug effects/*enzymology
MH  - PTEN Phosphohydrolase/*metabolism
MH  - Phosphatidylinositol 3-Kinases/*metabolism
MH  - Phosphatidylinositol 4,5-Diphosphate/metabolism
MH  - Phosphatidylinositol Phosphates/*metabolism
MH  - Phosphatidylinositol-3,4,5-Trisphosphate 5-Phosphatases
MH  - Phosphoric Monoester Hydrolases/*metabolism
MH  - Phosphorylation/drug effects
MH  - Protein Structure, Tertiary
MH  - Proto-Oncogene Proteins c-akt
MH  - Rats
MH  - Serum/*metabolism
PMC - PMC2169165
EDAT- 2007/09/26 09:00
MHDA- 2007/12/14 09:00
PMCR- 2008/04/01
CRDT- 2007/09/26 09:00
PHST- 2007/09/26 09:00 [pubmed]
PHST- 2007/12/14 09:00 [medline]
PHST- 2007/09/26 09:00 [entrez]
PHST- 2008/04/01 00:00 [pmc-release]
AID - MCB.00756-07 [pii]
AID - 0756-07 [pii]
AID - 10.1128/MCB.00756-07 [doi]
PST - ppublish
SO  - Mol Cell Biol. 2007 Dec;27(23):8098-112. doi: 10.1128/MCB.00756-07. Epub 2007 Sep 
      24.