PMID- 11792863
OWN - NLM
STAT- MEDLINE
DCOM- 20020429
LR  - 20211203
IS  - 0027-8424 (Print)
IS  - 1091-6490 (Electronic)
IS  - 0027-8424 (Linking)
VI  - 99
IP  - 2
DP  - 2002 Jan 22
TI  - Insulin-stimulated phosphorylation of lipin mediated by the mammalian target of 
      rapamycin.
PG  - 1047-52
AB  - The phosphorylation of a previously uncharacterized protein of apparent M(r) 
      approximately 140,000 was found to be increased when rat adipocytes were 
      incubated with insulin. The sequences of peptides generated by digesting the 
      protein with trypsin matched perfectly with sequences in mouse lipin. Lipin is 
      the product of the gene that is mutated in fatty liver dystrophy (fld) mice 
      [Peterfy, M., Phan, J., Xu, P. & Reue, K (2001) Nat. Genet. 27, 121-124], which 
      exhibit several phenotypic abnormalities including hyperlipidemia, defects in 
      adipocyte differentiation, impaired glucose tolerance, and slow growth. When 
      immunoblots were prepared with lipin antibodies, both endogenous adipocyte lipin 
      and recombinant lipin overexpressed in HEK293 cells appeared as bands ranging in 
      apparent M(r) from 120,000 to 140,000. Incubating adipocytes with insulin 
      decreased the electrophoretic mobility and stimulated the phosphorylation of both 
      Ser and Thr residues in lipin. The effects of insulin were abolished by 
      inhibitors of phosphatidylinositol 3-OH kinase, and by rapamycin, a specific 
      inhibitor of the mammalian target of rapamcyin (mTOR). The inhibition by 
      rapamycin was blocked by FK506, which competitively inhibits those effects of 
      rapamycin that are mediated by inhibition of mTOR. Moreover, amino acids, which 
      activate mTOR, mimicked insulin by increasing lipin phosphorylation in a 
      rapamycin-sensitive manner. Thus, lipin represents a target of the mTOR pathway, 
      and potentially links this nutrient-sensing pathway to adipocyte development.
FAU - Huffman, Todd A
AU  - Huffman TA
AD  - Department of Pharmacology, University of Virginia School of Medicine, 
      Charlottesville, VA 22908, USA.
FAU - Mothe-Satney, Isabelle
AU  - Mothe-Satney I
FAU - Lawrence, John C Jr
AU  - Lawrence JC Jr
LA  - eng
SI  - GENBANK/AF412811
GR  - R01 DK028312/DK/NIDDK NIH HHS/United States
GR  - R01 DK052753/DK/NIDDK NIH HHS/United States
GR  - DK28312/DK/NIDDK NIH HHS/United States
GR  - DK52723/DK/NIDDK NIH HHS/United States
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, P.H.S.
DEP - 20020115
PL  - United States
TA  - Proc Natl Acad Sci U S A
JT  - Proceedings of the National Academy of Sciences of the United States of America
JID - 7505876
RN  - 0 (Insulin)
RN  - 0 (Nuclear Proteins)
RN  - 0 (Proto-Oncogene Proteins)
RN  - 0 (Recombinant Proteins)
RN  - EC 2.7.- (Protein Kinases)
RN  - EC 2.7.1.1 (MTOR protein, human)
RN  - EC 2.7.1.1 (mTOR protein, mouse)
RN  - EC 2.7.1.1 (mTOR 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 (TOR Serine-Threonine Kinases)
RN  - EC 3.1.3.4 (LPIN1 protein, human)
RN  - EC 3.1.3.4 (Lpin1 protein, mouse)
RN  - EC 3.1.3.4 (Phosphatidate Phosphatase)
SB  - IM
MH  - Adipocytes/metabolism
MH  - Amino Acid Sequence
MH  - Animals
MH  - Cell Line
MH  - Humans
MH  - In Vitro Techniques
MH  - Insulin/*pharmacology
MH  - Male
MH  - Mice
MH  - Molecular Sequence Data
MH  - Molecular Weight
MH  - Nuclear Proteins/chemistry/genetics/*metabolism
MH  - Phosphatidate Phosphatase
MH  - Phosphorylation
MH  - Protein Kinases/*metabolism
MH  - *Protein Serine-Threonine Kinases
MH  - Proto-Oncogene Proteins/metabolism
MH  - Proto-Oncogene Proteins c-akt
MH  - Rats
MH  - Recombinant Proteins/chemistry/genetics/metabolism
MH  - Signal Transduction
MH  - TOR Serine-Threonine Kinases
PMC - PMC117427
EDAT- 2002/01/17 10:00
MHDA- 2002/05/01 10:01
PMCR- 2002/07/22
CRDT- 2002/01/17 10:00
PHST- 2002/01/17 10:00 [pubmed]
PHST- 2002/05/01 10:01 [medline]
PHST- 2002/01/17 10:00 [entrez]
PHST- 2002/07/22 00:00 [pmc-release]
AID - 022634399 [pii]
AID - 6343 [pii]
AID - 10.1073/pnas.022634399 [doi]
PST - ppublish
SO  - Proc Natl Acad Sci U S A. 2002 Jan 22;99(2):1047-52. doi: 10.1073/pnas.022634399. 
      Epub 2002 Jan 15.