PMID- 15886222
OWN - NLM
STAT- MEDLINE
DCOM- 20051028
LR  - 20211203
IS  - 0193-1849 (Print)
IS  - 0193-1849 (Linking)
VI  - 289
IP  - 4
DP  - 2005 Oct
TI  - Nutrient regulation of PKCepsilon is mediated by leucine, not insulin, in 
      skeletal muscle.
PG  - E684-94
AB  - Nutrients enhance signaling pathways involved in skeletal muscle growth through 
      an increased rate of protein synthesis. These studies have led to an 
      understanding of the potential role of the mammalian target of rapamycin (mTOR) 
      in this process. However, activation of mTOR cannot account for all the 
      stimulatory effects of nutrients. The purpose of these experiments was to examine 
      the effect of nutrients on the cellular distribution and activation state of 
      novel PKC isoforms (PKCepsilon and PKCdelta) in the gastrocnemius of rats by use 
      of modification state-dependent phosphopeptide-specific antibodies. The 
      phosphorylation of PKCepsilon on the catalytic domain autophosphorylation site 
      (Ser(729)) was elevated during feeding and then returned to basal levels when the 
      feeding period ended. Meal feeding augmented the phosphorylation of the 
      downstream effectors of mTOR, namely S6K1 and 4E-BP1. In contrast, the 
      phosphorylation of PKCdelta on either the catalytic domain autophosphorylation 
      site (Ser(643)) or activation loop site (Thr(505)) was unaffected. Similar 
      results were obtained when animals were given leucine either acutely via gavage 
      or chronically by dietary supplementations. The effect of leucine was not 
      mimicked by injecting animals with insulin but could be induced by gavage with 
      norleucine, a structural analog of leucine that does not increase plasma insulin 
      concentration. Thus rises in insulin secondary to meal intake or leucine gavage 
      are probably not responsible for increased phosphorylation of PKCepsilon in 
      response to meal feeding. Elevating the leucine concentration stimulated the 
      phosphorylation of PKCepsilon in gastrocnemius from perfused hindlimb and caused 
      a shift in the distribution of PKCepsilon from the membrane fraction to the 
      cytosolic fraction. The results indicate that leucine leads to an activation 
      (autophosphorylation) and subcellular redistribution of PKCepsilon, but not 
      PKCdelta, in gastrocnemius both in vivo and in vitro. Furthermore, activation of 
      the mTOR signaling pathway above basal conditions does not appear to be necessary 
      to induce phosphorylation or translocation of PKCepsilon, suggesting that 
      multiple signaling pathways become activated with leucine.
FAU - Vary, Thomas C
AU  - Vary TC
AD  - Dept. of Cellular and Molecular Physiology, Pennsylvania State University College 
      of Medicine, Hershey, PA 17033, USA. tvary@psu.edu
FAU - Goodman, Stacy
AU  - Goodman S
FAU - Kilpatrick, Laurie E
AU  - Kilpatrick LE
FAU - Lynch, Christopher J
AU  - Lynch CJ
LA  - eng
GR  - DK-053843/DK/NIDDK NIH HHS/United States
GR  - DK-062880/DK/NIDDK NIH HHS/United States
GR  - GM-34552/GM/NIGMS NIH HHS/United States
GR  - GM-39277/GM/NIGMS NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, U.S. Gov't, P.H.S.
DEP - 20050510
PL  - United States
TA  - Am J Physiol Endocrinol Metab
JT  - American journal of physiology. Endocrinology and metabolism
JID - 100901226
RN  - 0 (Insulin)
RN  - EC 2.7.- (Protein Kinases)
RN  - EC 2.7.1.- (Prkce protein, rat)
RN  - EC 2.7.1.1 (mTOR protein, rat)
RN  - EC 2.7.11.1 (TOR Serine-Threonine Kinases)
RN  - EC 2.7.11.13 (Protein Kinase C)
RN  - EC 2.7.11.13 (Protein Kinase C-epsilon)
RN  - GMW67QNF9C (Leucine)
SB  - IM
MH  - *Animal Nutritional Physiological Phenomena
MH  - Animals
MH  - Dose-Response Relationship, Drug
MH  - Insulin/*metabolism/*pharmacology
MH  - Leucine/*administration & dosage/*metabolism
MH  - Male
MH  - Muscle, Skeletal/drug effects/*metabolism
MH  - Phosphorylation/drug effects
MH  - Protein Kinase C/*metabolism
MH  - Protein Kinase C-epsilon
MH  - Protein Kinases/*metabolism
MH  - Rats
MH  - Rats, Sprague-Dawley
MH  - Signal Transduction/drug effects/physiology
MH  - TOR Serine-Threonine Kinases
EDAT- 2005/05/12 09:00
MHDA- 2005/10/29 09:00
CRDT- 2005/05/12 09:00
PHST- 2005/05/12 09:00 [pubmed]
PHST- 2005/10/29 09:00 [medline]
PHST- 2005/05/12 09:00 [entrez]
AID - 00613.2004 [pii]
AID - 10.1152/ajpendo.00613.2004 [doi]
PST - ppublish
SO  - Am J Physiol Endocrinol Metab. 2005 Oct;289(4):E684-94. doi: 
      10.1152/ajpendo.00613.2004. Epub 2005 May 10.