User:Peyton Jenkins/Sandbox 1
From Proteopedia
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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 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> | [[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> | ||
| - | + | ""'Add info about PJS'"" | |
== 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 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. | + | [[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. D98 forms a salt bridge with K78, further stabilizing the active site. R74 hydrogen bonds with Q251 of STRADα to stabilize the interaction between the two proteins. |
=== STRADα === | === STRADα === | ||
| - | The WEF motif (aa 429-431) on the C-terminus of STRADα with the C-terminus of MO25 | + | The WEF motif (aa 429-431) on the C-terminus of STRADα interacts with the C-terminus of MO25. |
== References == | == References == | ||
<references/> | <references/> | ||
Revision as of 01:02, 29 April 2025
2WTK: Hetertrimeric Complex of STK11, MO25, and STRADα
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