PMID- 22354785
OWN - NLM
STAT- MEDLINE
DCOM- 20120827
LR  - 20220408
IS  - 1522-1555 (Electronic)
IS  - 0193-1849 (Linking)
VI  - 302
IP  - 12
DP  - 2012 Jun 15
TI  - Role of PRAS40 in Akt and mTOR signaling in health and disease.
PG  - E1453-60
LID - 10.1152/ajpendo.00660.2011 [doi]
AB  - The proline-rich Akt substrate of 40 kDa (PRAS40) acts at the intersection of the 
      Akt- and mammalian target of rapamycin (mTOR)-mediated signaling pathways. The 
      protein kinase mTOR is the catalytic subunit of two distinct signaling complexes, 
      mTOR complex 1 (mTORC1) and mTORC2, that link energy and nutrients to the 
      regulation of cellular growth and energy metabolism. Activation of mTOR in 
      response to nutrients and growth factors results in the phosphorylation of 
      numerous substrates, including the phosphorylations of S6 kinase by mTORC1 and 
      Akt by mTORC2. Alterations in Akt and mTOR activity have been linked to the 
      progression of multiple diseases such as cancer and type 2 diabetes. Although 
      PRAS40 was first reported as substrate for Akt, investigations toward 
      mTOR-binding partners subsequently identified PRAS40 as both component and 
      substrate of mTORC1. Phosphorylation of PRAS40 by Akt and by mTORC1 itself 
      results in dissociation of PRAS40 from mTORC1 and may relieve an inhibitory 
      constraint on mTORC1 activity. Adding to the complexity is that gene silencing 
      studies indicate that PRAS40 is also necessary for the activity of the mTORC1 
      complex. This review summarizes the regulation and potential function(s) of 
      PRAS40 in the complex Akt- and mTOR-signaling network in health and disease.
FAU - Wiza, Claudia
AU  - Wiza C
AD  - Institute of Clinical Biochemistry and Pathobiochemistry, German Diabetes Center, 
      Dusseldorf, Germany.
FAU - Nascimento, Emmani B M
AU  - Nascimento EB
FAU - Ouwens, D Margriet
AU  - Ouwens DM
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20120221
PL  - United States
TA  - Am J Physiol Endocrinol Metab
JT  - American journal of physiology. Endocrinology and metabolism
JID - 100901226
RN  - 0 (AKT1S1 protein, human)
RN  - 0 (Adaptor Proteins, Signal Transducing)
RN  - 0 (CRTC1 protein, human)
RN  - 0 (Transcription Factors)
RN  - EC 2.7.1.1 (MTOR protein, human)
RN  - EC 2.7.11.1 (Proto-Oncogene Proteins c-akt)
RN  - EC 2.7.11.1 (TOR Serine-Threonine Kinases)
SB  - IM
MH  - Adaptor Proteins, Signal Transducing/biosynthesis/*genetics/*physiology
MH  - Animals
MH  - Conserved Sequence
MH  - Disease
MH  - Gene Expression Regulation/physiology
MH  - Health
MH  - Humans
MH  - Phosphorylation
MH  - Protein Binding
MH  - Proto-Oncogene Proteins c-akt/*physiology
MH  - Signal Transduction/*genetics/physiology
MH  - TOR Serine-Threonine Kinases/*physiology
MH  - Transcription Factors/genetics/physiology
EDAT- 2012/02/23 06:00
MHDA- 2012/08/28 06:00
CRDT- 2012/02/23 06:00
PHST- 2012/02/23 06:00 [entrez]
PHST- 2012/02/23 06:00 [pubmed]
PHST- 2012/08/28 06:00 [medline]
AID - ajpendo.00660.2011 [pii]
AID - 10.1152/ajpendo.00660.2011 [doi]
PST - ppublish
SO  - Am J Physiol Endocrinol Metab. 2012 Jun 15;302(12):E1453-60. doi: 
      10.1152/ajpendo.00660.2011. Epub 2012 Feb 21.