全 文 :Chinese Bulletin of Life Sciences
17 2
2005 4
Vol. 17, No. 2
Apr., 2005
AMPK
400038
AMP (AMP-activated protein kinase, AMPK)
ATP ATP
A M P K
A M P K A M P
Q555.7 A
Advances in the studies of AMP-activated protein kinase
FU Qing-Ying, GAO Yu-Qi*
(Key Laboratory of High Altitude Physiology and Mountain Sickness of PLA, Department of Pathophysiology and
High Altitude Physiology, Third Military Medical University, Chongqing 400038, China)
Abstract: The AMP-activated protein kinase is found in all eukaryotic cells. Once activated, the kinase switches
on ATP-producing catabolic pathways and switches off ATP-consuming processes,both via direct phosphory-
lation of downstream targets, and thus is called a cellular energy regulator . A variety of novel downstream
target proteins have been discovered recently, which provide new insight into elucidating precise functions of
AMP-activated protein kinase.
Key words: AMP-activated protein kinase; energy metabolism; adenosine monophosphate
AMPK
AMPK
ATP
ATP
AMPK
AMPK
1 AMPK
A M P K α ( 6 3 k D ) β ( 3 0 k D ) γ
(37~63kD) α
β γ
2004-07-19
30393131
( 1 9 7 7 ) ( 1 9 6 2 ) *
1004-0374(2005)02-0147-06
α1 α2 β1 β2 γ1 γ2 γ3 α
N C
N C β
γ C
AMP N C
α β γ AMPK
β γ
α
α β γ AMPK α
Thr172 β
N KIS
ASC ASC α β γ
· ·
148
[1] KIS
KIS N-
β
[2] γ N
γ1 γ2 γ3 N
γ CBS AMPK
AMP β γ
β N
γ N
AMPK
2 AMPK
AMPK α1
α 2
α2
[3] α2 α1
[4] α1 α2
A T P
AMPK-α2
[5] β1
β2 γ1 γ2
γ 3
AMPK
[6]
3 AMPK
3.1 AMP/ATP
A
AMP/ATP
AMPK
5 - - 4 - ( 5 -
amino-4-imidazolecarboxamide-riboside, AICAR)
AMPK AICAR
ZMP(5-aminoimidazole-4-carboxamide-1-β-D-
ribofuranosyl-5-monophate) ZMP AMP
AMPK AICAR AMPK
ZMP AMP (
-1, 6- )
3.2 AMP (leptin)
(adiponectin)
leptin
leptin
AMPK α2 leptin
-
leptin AMPK
[7] adiponectin
adiponectin
AMPK
[8~10] AMPK
2 ( ) [ 1 1 ]
ONOO-[12] [13] AMPK
AMP AMP/ATP
3.3 AMPK (AMP-activated protein kinase
kinase AMPKK)
AMPK AMPKK
LKB1
AMPKα Thr172
[14] LKB1
Thr172 AMPK
[15]
LKB1 STRADα/β
MO25α/β AMPK
[16] AMPK AMPK
LKB1
[17]
AMPK
C75
A T P
AMPK [18]
AMPK Compound C[11]
α
AMPK
4 AMPK
4.1 AMPK
4
4 [19]
AMPK AICAR
AMPK [20]
AMPK AICAR
AMPK
AMPK
AMPK
[21] AMPK
[ 2 2 ]
AMPK -2-
2, 6-
- 2 -
AMPK
AMPK
-2- ATP[ 2 3 ]
AMPK ( 1, 6-
)
4.2 CoA
CoA
AMPK AMPK
CoA
AMPK
4.3
(mammalian target of rapamycin,
mTOR) mRNA
mTOR mTOR
4E 70kD S6 S6
4G
[24]
AMPK mTOR AMPK
mTOR [25] AMPK
mTOR Horman [26]
AICAR AMPK
2(eukaryotic elongation fac-
tor-2, eEF-2) eEF-2
eEF-2 [27]
4.4 AMPK
p300 Ser89
p300 (
X ) p300
( E1a p53 GATA4)
[28]
1(hypoxia-inducible factor-1, HIF-1)
AMPK
HIF-1 AMPK
AMPK
HIF-1 AMPK
HIF-1
HIF-1
AMPK HIF-1
AMPK
HIF-1 AMPK HIF-1
3 /Akt
[29]
[30] AMPK
4α(hepatocyte nuclear factor-4α, HNF4α)
HNF4α
DNA HNF4α
HNF4α
HNF4α
HNF4α AMPK
AMPK -2
[31] γ 1α
[ 3 2 ] 1C
(sterol-regulatory-element-binding protein-1c, SREBP1c)
(fatty acid synthase, FAS)
SREBP1c FAS mRNA
[33]
L
L
[ 3 4 ]
4.5 AMPK
AICAR AMPK c-myc c-Jun N
caspase β
[35~36] caspase
[ 3 7 ]
AICAR AMPK κB(nuclear
factor-kappaB, NF-κB)
150
NF-κB AICAR [38] AMPK
4.6 AMPK
Akt AMPK
AMPK
[39] AMPK
[40]
[41]
4.7 AMPK cAMP
[42]
AICAR (
α 1β 6)
IκB α/β
NF-κB CCAAT/
(CCAAT/enhancer-binding protein, C/
E B P ) - ∆ C / E B P
AMPKα2 AMPKα2
A M P K
AMPK AMPK
[43~44]
4.8
(cystic fibrosis transmembrane conductance
regulator, CFTR) ATP Cl-
cAMP
A T P
ATP CFTR CFTR
AMPK
cAMP CFTR Cl-
AMPK
cAMP Cl- [45]
CFTR AMPK
AMPK
Na+ [46]
4.9 AMPK
AMPK AMPK
[47] AMPK
leptin AMPK agouti-
AMPK [7]
AMPK [48]
AMPK
β- p16INK4a
RNA HuR
AMPK HuR
HuR
AMPK
HuR
AMPK
[49]
5
AMPK AMPK
AMPK
AMPK
AMPK
AMPK
(1) AICAR AMPK
AICAR AMPK
AMPK AICAR
AMPK
AMPK
(2) AMPK
AMPKK
LKB1 AMPK
AMPK
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Karolinska Institutet 1
OX40L T
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