AMPK - Revision history

Akberdinir@gmail.com: /* Action */

2021-08-12T05:30:24Z

‎Action

Avertyshev@mail.ru at 14:02, 4 October 2018

2018-10-04T14:02:36Z

Avertyshev@mail.ru: /* Upstream */

2018-10-04T14:02:16Z

‎Upstream

Avertyshev@mail.ru: /* Upstream */

2018-10-04T14:01:49Z

‎Upstream

Avertyshev@mail.ru at 14:44, 25 September 2018

2018-09-25T14:44:51Z

Avertyshev@mail.ru at 14:54, 13 September 2018

2018-09-13T14:54:39Z

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Avertyshev@mail.ru: /* Upstream */

2018-05-30T14:21:31Z

‎Upstream

Avertyshev@mail.ru at 14:20, 30 May 2018

2018-05-30T14:20:30Z

Avertyshev@mail.ru at 14:16, 30 May 2018

2018-05-30T14:16:55Z

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Avertyshev@mail.ru at 16:21, 24 May 2018

2018-05-24T16:21:13Z

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 ===Action===
-AMPK, a fuel sensor and regulator, promotes ATP-producing and inhibits ATP-consuming pathways in various tissues. AMPK is exists as a heterotrimeric complex composed of a catalytic α subunit and regulatory β and γ subunits. The kinase is activated in response to stresses that deplete cellular ATP supplies such as low glucose, hypoxia, ischemia and heat shock. Binding of AMP to the γ subunit allosterically activates the complex, making it a more attractive substrate for its major upstream AMPK kinase, LKB1. As a cellular energy sensor responding to low ATP levels, AMPK activation positively regulates signaling pathways that replenish cellular ATP supplies. For example, activation of AMPK enhances both the transcription and translocation of GLUT4, resulting in an increase in insulin-stimulated glucose uptake. In addition, it also stimulates catabolic processes such as fatty acid oxidation and glycolysis via inhibition of ACC and activation of PFK2. AMPK negatively regulates several proteins central to ATP consuming processes such as TORC2, glycogen synthase, SREBP-1 and TSC2, resulting in the downregulation or inhibition of gluconeogenesis, glycogen, lipid and protein synthesis. Due to its role as a central regulator of both lipid and glucose metabolism, AMPK is considered to be a key therapeutic target for the treatment of obesity, type II diabetes mellitus, and cancer. The AMP-activated protein kinase (AMPK) has an important role in the regulation of cellular energy homeostasis. The enzyme is activated under conditions of low ATP, often caused by a variety of stresses and regulates signaling pathways that increase the supplies of ATP available. (http://www.sinobiological.com/ampk-signaling-pathwawy.html)
+AMPK, a fuel sensor and regulator, promotes ATP-producing and inhibits ATP-consuming pathways in various tissues. AMPK exists as a heterotrimeric complex composed of a catalytic α subunit and regulatory β and γ subunits. The kinase is activated in response to stresses that deplete cellular ATP supplies such as low glucose, hypoxia, ischemia and heat shock. Binding of AMP to the γ subunit allosterically activates the complex, making it a more attractive substrate for its major upstream AMPK kinase, LKB1. As a cellular energy sensor responding to low ATP levels, AMPK activation positively regulates signaling pathways that replenish cellular ATP supplies. For example, activation of AMPK enhances both the transcription and translocation of GLUT4, resulting in an increase in insulin-stimulated glucose uptake. In addition, it also stimulates catabolic processes such as fatty acid oxidation and glycolysis via inhibition of ACC and activation of PFK2. AMPK negatively regulates several proteins central to ATP consuming processes such as TORC2, glycogen synthase, SREBP-1 and TSC2, resulting in the downregulation or inhibition of gluconeogenesis, glycogen, lipid and protein synthesis. Due to its role as a central regulator of both lipid and glucose metabolism, AMPK is considered to be a key therapeutic target for the treatment of obesity, type II diabetes mellitus, and cancer. The AMP-activated protein kinase (AMPK) has an important role in the regulation of cellular energy homeostasis. The enzyme is activated under conditions of low ATP, often caused by a variety of stresses and regulates signaling pathways that increase the supplies of ATP available. (http://www.sinobiological.com/ampk-signaling-pathwawy.html)
 ===Kinetics===

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 AMPK
 Protein Kinase AMP-Activated
-Ver. 0.9.
+Ver. 1.0.
 ===Summary remarks===

← Older revision		Revision as of 14:02, 4 October 2018
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−	''' AMPK is phosphorylated and activated by ''' [[LKB1]] (LKB1/STRAD/MO25 complex), , [[CaMKKβ]]	+	''' AMPK is phosphorylated and activated by ''' [[LKB1]] (LKB1/STRAD/MO25 complex), [[CaMKKβ]]

	''' AMPK is phosphorylated and ingibited by ''' AKT, ROS, RNS, PKD1		''' AMPK is phosphorylated and ingibited by ''' AKT, ROS, RNS, PKD1

← Older revision		Revision as of 14:01, 4 October 2018
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−	''' AMPK is phosphorylated and activated by ''' LKB1 (LKB1/STRAD/MO25 complex), ~~CAMKK2~~	+	''' AMPK is phosphorylated and activated by ''' [[LKB1]] (LKB1/STRAD/MO25 complex), , [[CaMKKβ]]

	''' AMPK is phosphorylated and ingibited by ''' AKT, ROS, RNS, PKD1		''' AMPK is phosphorylated and ingibited by ''' AKT, ROS, RNS, PKD1

@@ Line 1,375: / Line 1,375: @@
 #3 pmid=17038425	<!-- Birk 2006 -->
 #4 pmid=19243572	<!-- Jensen 2009 -->
-#5 pmid=9693118	<!-- Salt 1998 -->
+#5 pmid=9693118	        <!-- Salt 1998 -->
 #6 pmid=12015362	<!-- Park 2002 -->
 #7 pmid=11052978	<!-- Chen 2000 -->

@@ Line 96: / Line 96: @@
 ====Upstream====
 '''AMPK is phosphorylated and activated by ''' LKB1 (LKB1/STRAD/MO25 complex), CAMKK2
@@ Line 105: / Line 106: @@
 (Morales-Alamo 2016) <cite>18</cite>.
 Reactive oxygen and nitrogen species (RONS) may activate AMPK by direct an indirect mechanisms. Directly, RONS may activate or deactivate AMPK by modifying RONS-sensitive residues of the AMPK-α subunit. Both too high (hypoxia) and too low (ingestion of antioxidants) RONS levels may lead to Ser485-AMPKα1/ Ser491-AMPKα2 phosphorylation causing inhibition of Thr172-AMPKα phosphorylation.
 (Kjøbsted 2018) <cite>55</cite>.
 After exercise and energy repletion, AMPK is converted back to an inactive form by dephosphorylation catalyzed by protein phosphatases (PP1A, PP2A, and PP2C) and undergoes inhibition by glycogen via binding to the GBD of the β subunit.
 In vitro or in non human muscle cells in some additional factors was identified:

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 ====Upstream====
-’’’AMPK is phosphorylated and activated by ’’’ LKB1 (LKB1/STRAD/MO25 complex), CAMKK2
+'''AMPK is phosphorylated and activated by ''' LKB1 (LKB1/STRAD/MO25 complex), CAMKK2
-’’’AMPK is phosphorylated and ingibited by ’’’ AKT, ROS, RNS, PKD1
+'''AMPK is phosphorylated and ingibited by ''' AKT, ROS, RNS, PKD1
-’’’AMPK is dephosphorylated by protein ’’’ PP1A, PP2A, PP2C
+'''AMPK is dephosphorylated by protein ''' PP1A, PP2A, PP2C
 (Morales-Alamo 2016) <cite>18</cite>.
@@ Line 310: / Line 310: @@
 |}
-’’’Other downstream targets, discovered not on human muscles. ’’’
+''' Other downstream targets, discovered not on human muscles. '''
 (Cantó 2010) <cite>17</cite>.