STK11

STK11
ساختارهای موجود
PDB	جستجوی هم‌ساخت‌شناسی: PDBe RCSB
فهرست شناسه‌های PDB
	2WTK, 4ZDR
معین‌کننده‌ها
نام‌های دیگر	STK11, LKB1, PJS, hLKB1, serine/threonine kinase 11
شناسه‌های بیرونی	OMIM: 602216 MGI: 1341870 HomoloGene: 393 GeneCards: STK11
موقعیت ژن (موش)
کروموزوم	کروموزوم ۱۰ (موش)
پایان	79,966,516 bp
الگوی گسترش RNA
	; ;
	More reference expression data
هستی‌شناسی ژن
عملکرد ملکولی	• transferase activity; • nucleotide binding; • LRR domain binding; • protein kinase activity; • p53 binding; • protein kinase activator activity; • metal ion binding; • kinase activity; • protein serine/threonine kinase activity; • GO:0001948، GO:0016582 پیوند پروتئینی; • ATP binding; • magnesium ion binding;
ترکیبات سلولی	• سیتوپلاسم; • membrane; • میتوکندری; • extracellular exosome; • TCR signalosome; • هسته یاخته; • نوکلئوپلاسم; • سیتوزول;
فرایند زیستی	• response to ionizing radiation; • positive regulation of transforming growth factor beta receptor signaling pathway; • dendrite extension; • TCR signalosome assembly; • axonogenesis; • glucose homeostasis; • positive regulation of autophagy; • فسفرگیری; • negative regulation of lipid biosynthetic process; • positive regulation of axonogenesis; • cellular response to DNA damage stimulus; • regulation of dendrite morphogenesis; • خودخواری; • protein phosphorylation; • Golgi localization; • regulation of Wnt signaling pathway; • vasculature development; • anoikis; • cellular response to UV-B; • negative regulation of cell growth; • regulation of cell growth; • tissue homeostasis; • establishment of cell polarity; • positive thymic T cell selection; • positive regulation of peptidyl-tyrosine phosphorylation; • regulation of protein kinase B signaling; • canonical Wnt signaling pathway; • intrinsic apoptotic signaling pathway by p53 class mediator; • protein autophosphorylation; • چرخه یاخته‌ای; • negative regulation of epithelial cell proliferation involved in prostate gland development; • T cell receptor signaling pathway; • اسپرماتوژنز; • activation of protein kinase activity; • negative regulation of TORC1 signaling; • negative regulation of cell population proliferation; • positive regulation of protein localization to nucleus; • GO:0097285 مرگ برنامه‌ریزی‌شده یاخته; • regulation of signal transduction by p53 class mediator; • جنین‌شناسی دستگاه عصبی مرکزی; • GO:0035404 peptidyl-serine phosphorylation; • peptidyl-threonine phosphorylation; • دگرگونی یاخته‌; • positive regulation of protein serine/threonine kinase activity; • GO:0016576 protein dephosphorylation; • negative regulation of canonical Wnt signaling pathway; • negative regulation of cold-induced thermogenesis;
	منابع: آمیگو / کوئیک‌گو
هم‌ساخت‌شناسی
	6794
	20869
	ENSG00000118046
	ENSMUSG00000003068
	Q15831
	Q9WTK7
	NM_000455
	NM_001301854، NM_011492، NR_126043، XM_006513439، XR_003948638، XR_004936136 NM_001301853، NM_001301854، NM_011492، NR_126043، XM_006513439، XR_003948638، XR_004936136
	NP_000446
	NP_001288783، NP_035622، XP_006513502 NP_001288782، NP_001288783، NP_035622، XP_006513502
	ویکی‌داده
مشاهده/ویرایش انسان	مشاهده/ویرایش موش

سرین/ترئونین کیناز ۱۱ (انگلیسی: Serine/threonine kinase 11) یا با اختصار «STK11» که با نام‌های کیناز بی۱ کبد (LKB1) و آنتی‌ژن NY-REN-19 کارسینوم کلیه هم شناخته می‌شود، یک آنزیم پروتئین کیناز است که در انسان توسط ژن «STK11» کُدگذاری می‌شود.^[۴] این ژن به خانوادهٔ پروتئین کینازهای اختصاصی سرین/ترئونین تعلق دارد که قطبیت سلول را تنظیم کرده و همچون یک «سرکوب‌گر تومور» عمل می‌کنند. جهش در این ژن سبب سرطان‌زایی می‌گردد.^[۵]

اهمیت بالینی

حداقل ۵۱ جهش بیماری‌زا در این ژن کشف شده است.^[۶] مثلاً جهش ژنی در سلول‌های زایا سبب سندرم پوتز-جگرز می‌گردد که در آن پولیپ‌های فراوان در دستگاه گوارش، ماکول‌های تیره رنگ پوستی-دهانی و نئوپلاسم‌های دیگر به وجود می‌آید.^[۷]^[۸]^[۹] با این حال، جهش‌های منفرد این ژن در سرطان ریه با منشأ پراکنده نیز دیده شده که عمدتاً آدنوکارسینوم بودند.^[۱۰] علاوه بر این، مطالعات اخیر تعداد زیادی جهش سوماتیک در این ژن را که در سرطان دهانه رحم، سرطان پستان،^[۱۱] سرطان روده، سرطان بیضه، سرطان لوزالمعده و سرطان پوست وجود دارد، کشف کرده‌اند.^[۱۲]^[۱۳]

این پروتئین به عنوان یک هدف بالقوه برای القای بازسازی سلول‌های ماهیچهٔ قلب پس از آسیب در نظر گرفته شده است زیرا امکان بازسازی قلب در پستانداران بالغ اندک است. سرکوب این ژن در قلب موش، فسفوریلاسیون AMPK را مهار کرد و پروتئین وابسته به YES را فعال کرد، که متعاقباً تکثیر سلول‌های ماهیچه‌های قلب را افزایش داد.^[۱۴]

منابع

↑ ^۱٫۰ ^۱٫۱ ^۱٫۲ GRCm38: Ensembl release 89: ENSMUSG00000003068 - Ensembl, May 2017
↑ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
↑ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
↑ Jenne DE, Reimann H, Nezu J, Friedel W, Loff S, Jeschke R, et al. (January 1998). "Peutz-Jeghers syndrome is caused by mutations in a novel serine threonine kinase". Nature Genetics. 18 (1): 38–43. doi:10.1038/ng0198-38. PMID 9425897. S2CID 28986057.
↑ Scott KD, Nath-Sain S, Agnew MD, Marignani PA (June 2007). "LKB1 catalytically deficient mutants enhance cyclin D1 expression". Cancer Research. 67 (12): 5622–7. doi:10.1158/0008-5472.CAN-07-0762. PMID 17575127.
↑ Šimčíková D, Heneberg P (December 2019). "Refinement of evolutionary medicine predictions based on clinical evidence for the manifestations of Mendelian diseases". Scientific Reports. 9 (1): 18577. Bibcode:2019NatSR...918577S. doi:10.1038/s41598-019-54976-4. PMC 6901466. PMID 31819097.
↑ Hemminki A, Tomlinson I, Markie D, Järvinen H, Sistonen P, Björkqvist AM, et al. (January 1997). "Localization of a susceptibility locus for Peutz-Jeghers syndrome to 19p using comparative genomic hybridization and targeted linkage analysis". Nature Genetics. 15 (1): 87–90. doi:10.1038/ng0197-87. PMID 8988175. S2CID 8978401.
↑ Hemminki A, Markie D, Tomlinson I, Avizienyte E, Roth S, Loukola A, et al. (January 1998). "A serine/threonine kinase gene defective in Peutz-Jeghers syndrome". Nature. 391 (6663): 184–7. Bibcode:1998Natur.391..184H. doi:10.1038/34432. PMID 9428765. S2CID 4400728.
↑ Scott R, Crooks R, Meldrum C (October 2008). "Gene symbol: STK11. Disease: Peutz-Jeghers Syndrome". Human Genetics. 124 (3): 300. doi:10.1007/s00439-008-0551-3. PMID 18846624.
↑ Sanchez-Cespedes M, Parrella P, Esteller M, Nomoto S, Trink B, Engles JM, et al. (July 2002). "Inactivation of LKB1/STK11 is a common event in adenocarcinomas of the lung". Cancer Research. 62 (13): 3659–62. PMID 12097271.
↑ Andrade-Vieira R, Xu Z, Colp P, Marignani PA (2013-02-22). "Loss of LKB1 expression reduces the latency of ErbB2-mediated mammary gland tumorigenesis, promoting changes in metabolic pathways". PLOS ONE. 8 (2): e56567. Bibcode:2013PLoSO...856567A. doi:10.1371/journal.pone.0056567. PMC 3579833. PMID 23451056.
↑ Sanchez-Cespedes M (December 2007). "A role for LKB1 gene in human cancer beyond the Peutz-Jeghers syndrome". Oncogene. 26 (57): 7825–32. doi:10.1038/sj.onc.1210594. PMID 17599048.
↑ "Distribution of somatic mutations in STK11". Catalogue of Somatic Mutations in Cancer. Wellcome Trust Genome Campus, Hinxton, Cambridge. Archived from the original on 2012-04-02. Retrieved 2009-11-11.
↑ Qu, Shuang; Liao, Qiao; Yu, Cheng; Chen, Yue; Luo, Han; Xia, Xuewei; He, Duofen; Xu, Zaicheng; Jose, Pedro A.; Li, Zhuxin; Wang, Wei Eric (2022-05-25). "LKB1 suppression promotes cardiomyocyte regeneration via LKB1-AMPK-YAP axis". Bosnian Journal of Basic Medical Sciences (به انگلیسی). 22 (5): 772–783. doi:10.17305/bjbms.2021.7225. ISSN 1840-4812. PMC 9519156. PMID 35490365. S2CID 248465561.

برای مطالعهٔ بیشتر

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Baas AF, Smit L, Clevers H (June 2004). "LKB1 tumor suppressor protein: PARtaker in cell polarity". Trends in Cell Biology. 14 (6): 312–9. doi:10.1016/j.tcb.2004.04.001. PMID 15183188.
Katajisto P, Vallenius T, Vaahtomeri K, Ekman N, Udd L, Tiainen M, Mäkelä TP (January 2007). "The LKB1 tumor suppressor kinase in human disease". Biochimica et Biophysica Acta (BBA) - Reviews on Cancer. 1775 (1): 63–75. doi:10.1016/j.bbcan.2006.08.003. PMID 17010524.
Bonaldo MF, Lennon G, Soares MB (September 1996). "Normalization and subtraction: two approaches to facilitate gene discovery". Genome Research. 6 (9): 791–806. doi:10.1101/gr.6.9.791. PMID 8889548.
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Nakagawa H, Koyama K, Miyoshi Y, Ando H, Baba S, Watatani M, et al. (August 1998). "Nine novel germline mutations of STK11 in ten families with Peutz-Jeghers syndrome". Human Genetics. 103 (2): 168–72. doi:10.1007/s004390050801. PMID 9760200. S2CID 23986504.
Mehenni H, Gehrig C, Nezu J, Oku A, Shimane M, Rossier C, et al. (December 1998). "Loss of LKB1 kinase activity in Peutz-Jeghers syndrome, and evidence for allelic and locus heterogeneity". American Journal of Human Genetics. 63 (6): 1641–50. doi:10.1086/302159. PMC 1377635. PMID 9837816.
Guldberg P, thor Straten P, Ahrenkiel V, Seremet T, Kirkin AF, Zeuthen J (March 1999). "Somatic mutation of the Peutz-Jeghers syndrome gene, LKB1/STK11, in malignant melanoma". Oncogene. 18 (9): 1777–80. doi:10.1038/sj.onc.1202486. PMID 10208439.
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این یک مقالهٔ خرد زیست‌شناسی مولکولی است. می‌توانید با گسترش آن به ویکی‌پدیا کمک کنید.

[refGRCm38Ensembl-1] ۱٫۰ ^۱٫۱ ^۱٫۲ GRCm38: Ensembl release 89: ENSMUSG00000003068 - Ensembl, May 2017

[2] "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.

[3] "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.

[pmid9425897-4] Jenne DE, Reimann H, Nezu J, Friedel W, Loff S, Jeschke R, et al. (January 1998). "Peutz-Jeghers syndrome is caused by mutations in a novel serine threonine kinase". Nature Genetics. 18 (1): 38–43. doi:10.1038/ng0198-38. PMID 9425897. S2CID 28986057.

[5] Scott KD, Nath-Sain S, Agnew MD, Marignani PA (June 2007). "LKB1 catalytically deficient mutants enhance cyclin D1 expression". Cancer Research. 67 (12): 5622–7. doi:10.1158/0008-5472.CAN-07-0762. PMID 17575127.

[Šimčíková_2019_-_supplementary_table_S7-6] Šimčíková D, Heneberg P (December 2019). "Refinement of evolutionary medicine predictions based on clinical evidence for the manifestations of Mendelian diseases". Scientific Reports. 9 (1): 18577. Bibcode:2019NatSR...918577S. doi:10.1038/s41598-019-54976-4. PMC 6901466. PMID 31819097.

[pmid8988175-7] Hemminki A, Tomlinson I, Markie D, Järvinen H, Sistonen P, Björkqvist AM, et al. (January 1997). "Localization of a susceptibility locus for Peutz-Jeghers syndrome to 19p using comparative genomic hybridization and targeted linkage analysis". Nature Genetics. 15 (1): 87–90. doi:10.1038/ng0197-87. PMID 8988175. S2CID 8978401.

[pmid9428765-8] Hemminki A, Markie D, Tomlinson I, Avizienyte E, Roth S, Loukola A, et al. (January 1998). "A serine/threonine kinase gene defective in Peutz-Jeghers syndrome". Nature. 391 (6663): 184–7. Bibcode:1998Natur.391..184H. doi:10.1038/34432. PMID 9428765. S2CID 4400728.

[pmid18846624-9] Scott R, Crooks R, Meldrum C (October 2008). "Gene symbol: STK11. Disease: Peutz-Jeghers Syndrome". Human Genetics. 124 (3): 300. doi:10.1007/s00439-008-0551-3. PMID 18846624.

[pmid=_12097271-10] Sanchez-Cespedes M, Parrella P, Esteller M, Nomoto S, Trink B, Engles JM, et al. (July 2002). "Inactivation of LKB1/STK11 is a common event in adenocarcinomas of the lung". Cancer Research. 62 (13): 3659–62. PMID 12097271.

[Andrade-Vieira_2013-11] Andrade-Vieira R, Xu Z, Colp P, Marignani PA (2013-02-22). "Loss of LKB1 expression reduces the latency of ErbB2-mediated mammary gland tumorigenesis, promoting changes in metabolic pathways". PLOS ONE. 8 (2): e56567. Bibcode:2013PLoSO...856567A. doi:10.1371/journal.pone.0056567. PMC 3579833. PMID 23451056.

[pmid=_17599048-12] Sanchez-Cespedes M (December 2007). "A role for LKB1 gene in human cancer beyond the Peutz-Jeghers syndrome". Oncogene. 26 (57): 7825–32. doi:10.1038/sj.onc.1210594. PMID 17599048.

[urlCatalogue_of_Somatic_Mutations_in_Cancer-13] "Distribution of somatic mutations in STK11". Catalogue of Somatic Mutations in Cancer. Wellcome Trust Genome Campus, Hinxton, Cambridge. Archived from the original on 2012-04-02. Retrieved 2009-11-11.

[14] Qu, Shuang; Liao, Qiao; Yu, Cheng; Chen, Yue; Luo, Han; Xia, Xuewei; He, Duofen; Xu, Zaicheng; Jose, Pedro A.; Li, Zhuxin; Wang, Wei Eric (2022-05-25). "LKB1 suppression promotes cardiomyocyte regeneration via LKB1-AMPK-YAP axis". Bosnian Journal of Basic Medical Sciences (به انگلیسی). 22 (5): 772–783. doi:10.17305/bjbms.2021.7225. ISSN 1840-4812. PMC 9519156. PMID 35490365. S2CID 248465561.

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