PMID- 11978788
OWN - NLM
STAT- MEDLINE
DCOM- 20020806
LR  - 20210209
IS  - 0021-9258 (Print)
IS  - 0021-9258 (Linking)
VI  - 277
IP  - 26
DP  - 2002 Jun 28
TI  - Activation of the ERK pathway and atypical protein kinase C isoforms in exercise- 
      and aminoimidazole-4-carboxamide-1-beta-D-riboside (AICAR)-stimulated glucose 
      transport.
PG  - 23554-62
AB  - Exercise increases glucose transport in muscle by activating 5'-AMP-activated 
      protein kinase (AMPK), but subsequent events are unclear. Presently, we examined 
      the possibility that AMPK increases glucose transport through atypical protein 
      kinase Cs (aPKCs) by activating proline-rich tyrosine kinase-2 (PYK2), ERK 
      pathway components, and phospholipase D (PLD). In mice, treadmill exercise 
      rapidly activated ERK and aPKCs in mouse vastus lateralis muscles. In rat 
      extensor digitorum longus (EDL) muscles, (a) AMPK activator, 
      5-aminoimidazole-4-carboxamide-1-beta-d-riboside (AICAR), activated PYK2, ERK and 
      aPKCs; (b) effects of AICAR on ERK and aPKCs were blocked by tyrosine kinase 
      inhibitor, genistein, and MEK1 inhibitor, PD98059; and (c) effects of AICAR on 
      aPKCs and 2-deoxyglucose (2-DOG) uptake were inhibited by genistein, PD98059, and 
      PLD-inhibitor, 1-butanol. Similarly, in L6 myotubes, (a) AICAR activated PYK2, 
      ERK, PLD, and aPKCs; (b) effects of AICAR on ERK were inhibited by genistein, 
      PD98059, and expression of dominant-negative PYK2; (c) effects of AICAR on PLD 
      were inhibited by MEK1 inhibitor UO126; (d) effects of AICAR on aPKCs were 
      inhibited by genistein, PD98059, 1-butanol, and expression of dominant-negative 
      forms of PYK2, GRB2, SOS, RAS, RAF, and ERK; and (e) effects of AICAR on 2DOG 
      uptake/GLUT4 translocation were inhibited by genistein, PD98059, UO126, 
      1-butanol, cell-permeable myristoylated PKC-zeta pseudosubstrate, and expression 
      of kinase-inactive RAF, ERK, and PKC-zeta. AMPK activator dinitrophenol had 
      effects on ERK, aPKCs, and 2-DOG uptake similar to those of AICAR. Our findings 
      suggest that effects of exercise on glucose transport that are dependent on AMPK 
      are mediated via PYK2, the ERK pathway, PLD, and aPKCs.
FAU - Chen, Hubert C
AU  - Chen HC
AD  - James A. Haley Veterans Hospital and the Department of Internal Medicine, 
      University of South Florida College of Medicine, Tampa, Florida 33612, USA.
FAU - Bandyopadhyay, Gautam
AU  - Bandyopadhyay G
FAU - Sajan, Mini P
AU  - Sajan MP
FAU - Kanoh, Yoshinori
AU  - Kanoh Y
FAU - Standaert, Mary
AU  - Standaert M
FAU - Farese, Robert V Jr
AU  - Farese RV Jr
FAU - Farese, Robert V
AU  - Farese RV
LA  - eng
GR  - R01 DK065969/DK/NIDDK NIH HHS/United States
PT  - Journal Article
DEP - 20020426
PL  - United States
TA  - J Biol Chem
JT  - The Journal of biological chemistry
JID - 2985121R
RN  - 0 (Isoenzymes)
RN  - 0 (Ribonucleotides)
RN  - 360-97-4 (Aminoimidazole Carboxamide)
RN  - EC 2.7.11.13 (Protein Kinase C)
RN  - EC 2.7.11.24 (Mitogen-Activated Protein Kinases)
RN  - EC 3.1.4.4 (Phospholipase D)
RN  - F0X88YW0YK (AICA ribonucleotide)
RN  - IY9XDZ35W2 (Glucose)
SB  - IM
MH  - Aminoimidazole Carboxamide/*analogs & derivatives/*pharmacology
MH  - Animals
MH  - Biological Transport/drug effects
MH  - Enzyme Activation
MH  - Glucose/*metabolism
MH  - Isoenzymes/*physiology
MH  - Male
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Mitogen-Activated Protein Kinases/*physiology
MH  - Muscle, Skeletal/drug effects/metabolism
MH  - Phospholipase D/physiology
MH  - *Physical Conditioning, Animal
MH  - Protein Kinase C/*physiology
MH  - Rats
MH  - Rats, Sprague-Dawley
MH  - Ribonucleotides/*pharmacology
EDAT- 2002/04/30 10:00
MHDA- 2002/08/07 10:01
CRDT- 2002/04/30 10:00
PHST- 2002/04/30 10:00 [pubmed]
PHST- 2002/08/07 10:01 [medline]
PHST- 2002/04/30 10:00 [entrez]
AID - S0021-9258(19)66733-5 [pii]
AID - 10.1074/jbc.M201152200 [doi]
PST - ppublish
SO  - J Biol Chem. 2002 Jun 28;277(26):23554-62. doi: 10.1074/jbc.M201152200. Epub 2002 
      Apr 26.