AMPK signaling pathway: Difference between revisions
New page: <StructureSection load='4rer' size='350' side='right' scene='49/493732/Cv/1' caption='Human AMP-activated protein kinase α1 subunit (deeppink) +β2 subunit (green) +γ1 subunit (cyan) com... |
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<StructureSection load='4rer' size='350' side='right' scene='49/493732/Cv/1' caption='Human AMP-activated protein kinase α1 subunit (deeppink) +β2 subunit (green) +γ1 subunit (cyan) complex with AMP, staurosporine, cyclodextrin and HEPES (PDB code [[4rer]])'> | <StructureSection load='4rer' size='350' side='right' scene='49/493732/Cv/1' caption='Human AMP-activated protein kinase α1 subunit (deeppink) +β2 subunit (green) +γ1 subunit (cyan) complex with AMP, staurosporine, cyclodextrin and HEPES (PDB code [[4rer]])'> | ||
=Activation AMPK via Receptor tyrosine kinases/Ras/B-Raf= | |||
==[[Receptor tyrosine kinases]]== | |||
==Ras activation== | |||
[[GTPase KRas]] | |||
[[Allosteric modulation of H-Ras GTPase]] | |||
== | ==B-Raf== | ||
'''B-Raf''' is related to retroviral oncogenes and participates in cellular signal transduction. B-Raf domains include the kinase domain - residues 444-721 and Ras-binding domain - residues 153-237. Mutated B-Raf was found in some human cancers<ref>PMID:12460918</ref>. See more in [[B-RAF with PLX4032]]. | |||
==[[AMP-activated protein kinase]]== | |||
'''AMP-activated protein kinase''' (AMPK) is a [[nuclear receptor]] which regulates cellular uptake of glucose, β-oxidation of fatty acids and biogenesis of glucose transporter thus playing a role in cellular energy homeostasis by phosphorylating key proteins. In response to low levels of ATP, AMPK activates energy-producing pathways and inhibits energy-consuming pathways. | |||
AMPK is an important drug target for obesity, type 2 diabetes and cancer. AMPK activity is enhanced during exercise resulting in increased glucose uptake and blood supply in muscles. Stresses like hypoglycemia, anoxia and ischemia produce increase in AMPK levels.<br /> | |||
AMPK is a heterotrimer: <br /> <scene name='49/493732/Cv/10'>AMPK α subunit</scene> is the catalytic subunit and contains <scene name='49/493732/Cv/11'>Thr174 (TPO) which undergoes phosphorylation</scene>. <br /> <scene name='49/493732/Cv/5'>AMPK β subunit</scene> is a scaffold on which the heterotrimer assembles. There are 2 β subunits. β subunit contains <scene name='49/493732/Cv/12'>phosphorylated Ser108 (SEP)</scene>. <br /> <scene name='49/493732/Cv/8'>AMPK γ subunit</scene> detects shifts in AMP:ATP ratio via its 4 cystathionine β synthase (CBS) domains. <scene name='49/493732/Cv/13'>The active site binds 3 AMPs</scene>.<ref>PMID:25412657</ref> | |||
[[HMG-CoA Reductase]] is phosphorylated and inactivated by an AMP-activated protein kinase, when the energy charge of the cell is low and AMP concentrations are high. | |||
</StructureSection> | </StructureSection> | ||
== References == | == References == | ||
<references/> | <references/> | ||
Latest revision as of 16:27, 29 March 2022
Activation AMPK via Receptor tyrosine kinases/Ras/B-RafReceptor tyrosine kinasesRas activationAllosteric modulation of H-Ras GTPase B-RafB-Raf is related to retroviral oncogenes and participates in cellular signal transduction. B-Raf domains include the kinase domain - residues 444-721 and Ras-binding domain - residues 153-237. Mutated B-Raf was found in some human cancers[1]. See more in B-RAF with PLX4032. AMP-activated protein kinaseAMP-activated protein kinase (AMPK) is a nuclear receptor which regulates cellular uptake of glucose, β-oxidation of fatty acids and biogenesis of glucose transporter thus playing a role in cellular energy homeostasis by phosphorylating key proteins. In response to low levels of ATP, AMPK activates energy-producing pathways and inhibits energy-consuming pathways. AMPK is an important drug target for obesity, type 2 diabetes and cancer. AMPK activity is enhanced during exercise resulting in increased glucose uptake and blood supply in muscles. Stresses like hypoglycemia, anoxia and ischemia produce increase in AMPK levels. AMPK is a heterotrimer: HMG-CoA Reductase is phosphorylated and inactivated by an AMP-activated protein kinase, when the energy charge of the cell is low and AMP concentrations are high.
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ReferencesReferences
- ↑ Brose MS, Volpe P, Feldman M, Kumar M, Rishi I, Gerrero R, Einhorn E, Herlyn M, Minna J, Nicholson A, Roth JA, Albelda SM, Davies H, Cox C, Brignell G, Stephens P, Futreal PA, Wooster R, Stratton MR, Weber BL. BRAF and RAS mutations in human lung cancer and melanoma. Cancer Res. 2002 Dec 1;62(23):6997-7000. PMID:12460918
- ↑ Li X, Wang L, Zhou XE, Ke J, de Waal PW, Gu X, Tan MH, Wang D, Wu D, Xu HE, Melcher K. Structural basis of AMPK regulation by adenine nucleotides and glycogen. Cell Res. 2014 Nov 21. doi: 10.1038/cr.2014.150. PMID:25412657 doi:http://dx.doi.org/10.1038/cr.2014.150