[{"data":1,"prerenderedAt":-1},["ShallowReactive",2],{"detail-sidebar-cat-0-en-105":3,"doc-seo-366596-105":59,"doc-detail-366596-en":131},{"code":4,"msg":5,"data":6},0,"success",[7,13,18,23,28,33,38,43,48,51,55],{"id":8,"doc_module":4,"doc_module_name":9,"category_name":10,"show_sort_weight":11,"slug":12},1,"Document","Story & Novel",90,"story-novel",{"id":14,"doc_module":4,"doc_module_name":9,"category_name":15,"show_sort_weight":16,"slug":17},2,"Literature",80,"literature",{"id":19,"doc_module":4,"doc_module_name":9,"category_name":20,"show_sort_weight":21,"slug":22},4,"Exam",70,"exam",{"id":24,"doc_module":4,"doc_module_name":9,"category_name":25,"show_sort_weight":26,"slug":27},5,"Comic",60,"comic",{"id":29,"doc_module":4,"doc_module_name":9,"category_name":30,"show_sort_weight":31,"slug":32},6,"Technology",50,"technology",{"id":34,"doc_module":4,"doc_module_name":9,"category_name":35,"show_sort_weight":36,"slug":37},7,"Healthcare",40,"healthcare",{"id":39,"doc_module":4,"doc_module_name":9,"category_name":40,"show_sort_weight":41,"slug":42},8,"Research & Report",30,"research-report",{"id":44,"doc_module":4,"doc_module_name":9,"category_name":45,"show_sort_weight":46,"slug":47},9,"Religion & Spirituality",20,"religion-spirituality",{"id":46,"doc_module":4,"doc_module_name":9,"category_name":49,"show_sort_weight":46,"slug":50},"World Cup","world-cup",{"id":52,"doc_module":4,"doc_module_name":9,"category_name":53,"show_sort_weight":52,"slug":54},10,"Lifestyle","lifestyle",{"id":56,"doc_module":4,"doc_module_name":9,"category_name":57,"show_sort_weight":24,"slug":58},19,"General","general",{"code":4,"msg":60,"data":61},"ok",{"site_id":62,"language":63,"slug":64,"title":65,"keywords":66,"description":67,"schema_data":68,"social_meta":124,"head_meta":126,"extra_data":128,"updated_unix":130},105,"en","nuak-kinases-signaling-mechanisms-and-therapeutic-applications","NUAK kinases - Signaling mechanisms and therapeutic applications","","NUAK1 and NUAK2 are reviewed as two of the 12 adenosine monophosphate-activated protein-related kinases involved in cancer progression and in neurologic, fibrotic, and inflammatory diseases. The review summarizes protein structure, upstream regulators, downstream targets, and expression profiles across cancerous versus noncancerous tissues, and maps signaling pathways across multiple malignancies. It also compiles preclinical small-molecule NUAK inhibitors and reports one inhibitor in clinical trials, emphasizing selective therapeutic targeting.",{"@graph":69,"@context":123},[70,84,106],{"@type":71,"itemListElement":72},"BreadcrumbList",[73,77,79,82],{"item":74,"name":75,"@type":76,"position":8},"https://docshare.wps.com","Home","ListItem",{"item":78,"name":9,"@type":76,"position":14},"https://docshare.wps.com/document/",{"item":80,"name":35,"@type":76,"position":81},"https://docshare.wps.com/document/healthcare/",3,{"item":83,"name":65,"@type":76,"position":19},"https://docshare.wps.com/document/nuak-kinases-signaling-mechanisms-and-therapeutic-applications/366596/",{"url":83,"name":65,"@type":85,"image":86,"author":91,"headline":65,"publisher":94,"fileFormat":97,"inLanguage":63,"description":67,"dateModified":98,"datePublished":99,"encodingFormat":97,"isAccessibleForFree":100,"interactionStatistic":101},"DigitalDocument",{"url":87,"@type":88,"width":89,"height":90},"https://docshare.wps.com/thumbnails/nuak-kinases-signaling-mechanisms-and-therapeutic-applications/366596.png","ImageObject",300,407,{"name":92,"@type":93},"Aldword","Person",{"url":74,"name":95,"@type":96},"DocShare","Organization","application/pdf","2026-10-28","2026-09-23",true,{"@type":102,"interactionType":103,"userInteractionCount":105},"InteractionCounter",{"@type":104},"ViewAction",12,{"@type":107,"mainEntity":108},"FAQPage",[109,115,119],{"name":110,"@type":111,"acceptedAnswer":112},"What are NUAK1 and NUAK2 and why are they important?","Question",{"text":113,"@type":114},"NUAK1 and NUAK2 are novel (nua) kinases involved in signaling pathways linked to cancer progression and other disorders, including neurologic, fibrotic, and inflammatory diseases.","Answer",{"name":116,"@type":111,"acceptedAnswer":117},"What does the review cover about NUAK biology?",{"text":118,"@type":114},"It summarizes protein structure, upstream regulators, downstream targets, expression profiles in cancerous versus noncancerous tissue, and the biological roles and signaling pathways of NUAK kinases.",{"name":120,"@type":111,"acceptedAnswer":121},"How are NUAK kinases being targeted therapeutically?",{"text":122,"@type":114},"The review summarizes known small-molecule NUAK inhibitors in preclinical models and highlights one inhibitor currently in clinical trials, focusing on therapeutic potential of selective NUAK inhibition.","https://schema.org",{"og:url":83,"og:type":125,"og:title":65,"og:site_name":95,"og:description":67},"article",{"robots":127,"canonical":83},"index,follow",{"doc_id":129,"site_id":62},366596,1790612526,{"code":4,"msg":5,"data":132},{"doc_id":129,"user_id":133,"nickname":92,"user_avatar":134,"doc_module":4,"category_id":34,"category_name":35,"doc_title":65,"doc_description":67,"doc_content":135,"file_id":136,"file_url":137,"file_type":138,"file_size":139,"view_count":105,"is_deleted":4,"is_public":8,"is_downloadable":8,"audit_status":8,"page_count":56,"language":140,"language_code":63,"site_id":62,"html_lang":63,"table_of_contents":141,"faqs":142,"seo_title":143,"seo_description":67,"update_tm":144,"read_time":145},2336478940917,"https://ap-avatar.wpscdn.com/davatar_6f874abed73319feea01a86fa6f0fab8","REVIEWS  \nNUAK kinases: Signaling mechanisms and therapeutic applications  \nReceived for publication, April 23, 2025, and in revised form, July 7, 2025 Published, Papers in Press, August 5, 2025 [https://doi.org/10.1016/j.jbc.2025.1](https://doi.org/10.1016/j.jbc.2025.1)10565  \nNicole M. Cullen 1, Peter Rosston2,3, Bakhtawar Tufail 1, Anne E. D’Armond 1, Ayushi Patel4,5,  \nDara H. Khosravi6, Bridgette M. Collins-Burow7, Van T. Hoang 1,7, Elizabeth C. Martin 1,7, David H. Drewry2,8, Matthew E. Burow 1,7,*, and Suresh K. Alahari9,10,*  \nFrom the 1Department of Medicine, Section of Hematology and Oncology, Tulane University School of Medicine, New Orleans, Louisiana, USA; 2Structural Genomics Consortium, UNC Eshelman School of Pharmacy, and 3Department of Chemistry, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA; 4Cardiovascular Center of Excellence, and 5Department of Pharmacology and Experimental Therapeutics, Louisiana State University Health Sciences Center, New Orleans, Louisiana, USA; 6School of Medicine, LSU Health Science Center, New Orleans, Louisiana, USA; 7Tulane Cancer Center, Tulane University, New Orleans, Louisiana, USA; 8UNC Lineberger Comprehensive Cancer Center, School of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA; 9Department of Biochemistry and Molecular Biology, and 10Stanley S.  \nScott Cancer Center, LSU Health Science Center School of Medicine, New Orleans, Louisiana, USA Reviewed by members of the JBC Editorial Board. Edited by Brian D. Strahl  \nThe novel (nua) kinases 1 and 2 are two of 12 AMPactivated protein–related kinases whose signaling pathways are involved in cancer progression, as well as neurologic, fibrotic, and inflammatory diseases. Currently, there are 80 Food and Drug Administration-approved kinase inhibitors which target roughly 24 of the 500+ known human kinases, leaving most kinases underexplored, including NUAK1 and NUAK2. Thus, there is a critical need for selective inhibition of NUAK1 and NUAK2 signaling. Here, we review the protein structure, known upstream regulators and downstream targets, and expression profiles of NUAK1 and NUAK2 in cancerous compared to noncancerous tissue. We also delineate the biological roles and signaling pathways of the NUAK kinases in a range of malignancies, focusing on cancer but also covering noncancerous physiology, and the therapeutic potential of NUAK kinase inhibition. We summarize the known small-molecule NUAK kinase inhibitors in preclinical models and one inhibitor in clinical trials. This review highlights the signaling mechanisms and therapeutic value of targeting NUAK kinase signaling pathways with specific, small-molecule NUAK inhibitors.  \nAdenosine monophosphate-activated protein kinase (AMPK) is a serine/threonine protein kinase, key cellular metabolic sensor, and mediator of cell proliferation and polarity (1, 2). Notably, there are 12 AMP-activated protein– related kinases (ARKs), including novel (nua) kinase 1 (NUAK1) and 2 (NUAK2) which are involved in a broad range of biological and physiological roles. In humans, the NUAK1 gene is located on chromosome 12 and encodes a protein of 661 amino acids (Fig. 1A) with an estimated molecular weight of 76 kDa (3). The NUAK2 gene is found on chromosome 1 of  \n* For correspondence: Matthew E. Burow, [mburow@tulane.edu](mburow@tulane.edu); Suresh K. Alahari, [salaha@lsuhsc.edu](salaha@lsuhsc.edu).  \nthe human genome and encodes a protein of 628 amino acids (Fig. 1B) with an estimated molecular weight of 70 kDa (3). NUAK1 and NUAK2 exhibit 58% homology in their amino acid protein sequences (3, 4), exhibit similar structural organization to the other members of the ARKs, and demonstrate sequence homology with the catalytic subunit of AMPK (5). Like the other ARK family members, NUAK1 and NUAK2 contain an N-terminal catalytic domain with a highly conserved activation T-loop and a noncatalytic C-terminal domain with a spacer s","cbCaica0L9rMVZJ0","https://ap.wps.com/l/cbCaica0L9rMVZJ0","pdf",3258678,"English","# Overview and significance of NUAK kinases\n## Biological roles across diseases\n# Molecular features and structural organization\n## Domains, regulation, and homology\n# Signaling pathways and disease connections\n# Therapeutic targeting and inhibitors","[{\"question\":\"What are NUAK1 and NUAK2 and why are they important?\",\"answer\":\"NUAK1 and NUAK2 are novel (nua) kinases involved in signaling pathways linked to cancer progression and other disorders, including neurologic, fibrotic, and inflammatory diseases.\"},{\"question\":\"What does the review cover about NUAK biology?\",\"answer\":\"It summarizes protein structure, upstream regulators, downstream targets, expression profiles in cancerous versus noncancerous tissue, and the biological roles and signaling pathways of NUAK kinases.\"},{\"question\":\"How are NUAK kinases being targeted therapeutically?\",\"answer\":\"The review summarizes known small-molecule NUAK inhibitors in preclinical models and highlights one inhibitor currently in clinical trials, focusing on therapeutic potential of selective NUAK inhibition.\"}]","NUAK kinases - Signaling mechanisms and therapeutic applications | PDF",1790166329,48]