User:Peyton Jenkins/Sandbox 1
From Proteopedia
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== Relevance and Disease == | == Relevance and Disease == | ||
Lung cancer is the leading cause of cancer related death worldwide. In the United States alone, over 120,000 deaths were caused by lung cancer in 2024<ref>https://www.cancer.org/content/dam/cancer-org/research/cancer-facts-and-statistics/annual-cancer-facts-and-figures/2024/2024-cancer-facts-and-figures-acs.pdf</ref>. Non small cell lung cancer make up approximately 84% of all lung cancer cases, and of these lung adenocarcinoma accounts for about 65%<ref>10.1001/jamaoncol.2021.4932</ref>. In lung adenocarcinoma, ''STK11'' is the third most commonly mutated gene, behind only ''KRAS'' and ''p53''<ref>10.1091/mbc.E15-08-0569.</ref>. | Lung cancer is the leading cause of cancer related death worldwide. In the United States alone, over 120,000 deaths were caused by lung cancer in 2024<ref>https://www.cancer.org/content/dam/cancer-org/research/cancer-facts-and-statistics/annual-cancer-facts-and-figures/2024/2024-cancer-facts-and-figures-acs.pdf</ref>. Non small cell lung cancer make up approximately 84% of all lung cancer cases, and of these lung adenocarcinoma accounts for about 65%<ref>10.1001/jamaoncol.2021.4932</ref>. In lung adenocarcinoma, ''STK11'' is the third most commonly mutated gene, behind only ''KRAS'' and ''p53''<ref>10.1091/mbc.E15-08-0569.</ref>. | ||
| - | [[STK11]] is a master kinase, signalling upstream of [[AMPK]] family kinases, [[p53]], and [[FAK]], to regulate processes like anoikis, adhesion, growth, metabolism, and survival<ref>10.1038/sj.emboj.7600110</ref><sup>, </sup><ref>10.1074/jbc.M112.444620</ref>. [STK11] exists in a heterotrimeric complex with the pseudokinase | + | [[STK11]] is a master kinase, signalling upstream of [[AMPK]] family kinases, [[p53]], and [[FAK]], to regulate processes like anoikis, adhesion, growth, metabolism, and survival<ref>10.1038/sj.emboj.7600110</ref><sup>, </sup><ref>10.1074/jbc.M112.444620</ref>. [[STK11]] exists in a heterotrimeric complex with the pseudokinase STRADα, and the scaffolding protein MO25. This complex is essential for both proper kinase activity and proper localization. <ref>10.1038/sj.emboj.7600110</ref><sup>, </sup> <ref>10.1093/emboj/cdg490</ref> |
== Structural Highlights == | == Structural Highlights == | ||
=== STK11: === | === STK11: === | ||
| - | [[STK11]] can be broken down into 3 domains. An N-terminal domain (aa 1-42), kinase domain (aa 43-347), and a C-terminal domain (aa 348-433). The | + | [[STK11]] can be broken down into 3 domains. An N-terminal domain (aa 1-42), kinase domain (aa 43-347), and a C-terminal domain (aa 348-433). The activation loop of [[STK11]] is located from residues ~202-212. Within the activation loop is P204, which interacts with a hydrophobic pocket on MO25, which is necessary to stabilize the active conformation. |
=== Holding the complex together === | === Holding the complex together === | ||
The C-terminus of MO25 interacts with a WEF motif (aa 429-431) on the C-terminus of STRADα. | The C-terminus of MO25 interacts with a WEF motif (aa 429-431) on the C-terminus of STRADα. | ||
Revision as of 00:22, 29 April 2025
2WTK: Hetertrimeric Complex of STK11, MO25, and STRADα
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