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Conserved regulatory motifs in the juxtamembrane domain and kinase N-lobe revealed through deep mutational scanning of the MET receptor tyrosine kinase domain.

التفاصيل البيبلوغرافية
العنوان: Conserved regulatory motifs in the juxtamembrane domain and kinase N-lobe revealed through deep mutational scanning of the MET receptor tyrosine kinase domain.
المؤلفون: Estevam GO; Department of Bioengineering and Therapeutic Sciences, University of California, San Francisco, San Francisco,United States.; Tetrad Graduate Program, University of California San Francisco, San Francisco, United States., Linossi EM; Cardiovascular Research Institute, University of California San Francisco, San Francisco, United States.; Department of Cellular and Molecular Pharmacology, University of California San Francisco, United States., Macdonald CB; Department of Bioengineering and Therapeutic Sciences, University of California, San Francisco, San Francisco,United States., Espinoza CA; Tetrad Graduate Program, University of California San Francisco, San Francisco, United States.; Cardiovascular Research Institute, University of California San Francisco, San Francisco, United States.; Department of Cellular and Molecular Pharmacology, University of California San Francisco, United States., Michaud JM; Department of Bioengineering and Therapeutic Sciences, University of California, San Francisco, San Francisco,United States., Coyote-Maestas W; Department of Bioengineering and Therapeutic Sciences, University of California, San Francisco, San Francisco,United States.; Quantitative Biosciences Institute, University of California, San Francisco, United States, United States., Collisson EA; Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco, United States.; Department of Medicine/Hematology and Oncology, University of California, San Francisco, United States., Jura N; Cardiovascular Research Institute, University of California San Francisco, San Francisco, United States.; Department of Cellular and Molecular Pharmacology, University of California San Francisco, United States.; Quantitative Biosciences Institute, University of California, San Francisco, United States, United States., Fraser JS; Department of Bioengineering and Therapeutic Sciences, University of California, San Francisco, San Francisco,United States.; Quantitative Biosciences Institute, University of California, San Francisco, United States, United States.
المصدر: BioRxiv : the preprint server for biology [bioRxiv] 2024 May 06. Date of Electronic Publication: 2024 May 06.
نوع المنشور: Preprint
اللغة: English
بيانات الدورية: Country of Publication: United States NLM ID: 101680187 Publication Model: Electronic Cited Medium: Internet ISSN: 2692-8205 (Electronic) Linking ISSN: 26928205 NLM ISO Abbreviation: bioRxiv Subsets: PubMed not MEDLINE
مستخلص: MET is a receptor tyrosine kinase (RTK) responsible for initiating signaling pathways involved in development and wound repair. MET activation relies on ligand binding to the extracellular receptor, which prompts dimerization, intracellular phosphorylation, and recruitment of associated signaling proteins. Mutations, which are predominantly observed clinically in the intracellular juxtamembrane and kinase domains, can disrupt typical MET regulatory mechanisms. Understanding how juxtamembrane variants, such as exon 14 skipping (METΔEx14), and rare kinase domain mutations can increase signaling, often leading to cancer, remains a challenge. Here, we perform a parallel deep mutational scan (DMS) of the MET intracellular kinase domain in two fusion protein backgrounds: wild type and METΔEx14. Our comparative approach has revealed a critical hydrophobic interaction between a juxtamembrane segment and the kinase αC-helix, pointing to potential differences in regulatory mechanisms between MET and other RTKs. Additionally, we have uncovered a β5 motif that acts as a structural pivot for the kinase domain in MET and other TAM family of kinases. We also describe a number of previously unknown activating mutations, aiding the effort to annotate driver, passenger, and drug resistance mutations in the MET kinase domain.
Competing Interests: Competing Interests JSF is a consultant for, has equity in, and receives research support from Relay Therapeutics. N.J. is a founder of Rezo Therapeutics and a shareholder of Rezo Therapeutics, Sudo Therapeutics, and Type6 Therapeutics. N.J. is a SAB member of Sudo Therapeutics, Type6 Therapeutic and NIBR Oncology. The Jura laboratory has received sponsored research support from Genentech, Rezo Therapeutics and Type6 Therapeutics. E.A.C. is a consultant at IHP Therapeutics, Valar Labs, Tatara Therapeutics and Pear Diagnostics, reports receiving commercial research grants from Pfizer, and has stock ownership in Tatara Therapeutics, HDT Bio, Clara Health, Aqtual, and Guardant Health.
References: Structure. 2017 Jun 6;25(6):867-877.e3. (PMID: 28528776)
Nucleic Acids Res. 2023 Jan 6;51(D1):D523-D531. (PMID: 36408920)
Cell. 2006 Jun 16;125(6):1137-49. (PMID: 16777603)
J Biol Chem. 2006 Nov 3;281(44):33577-87. (PMID: 16928683)
J Biol Chem. 1991 Nov 25;266(33):22087-90. (PMID: 1718989)
Mol Cell. 2019 Apr 18;74(2):393-408.e20. (PMID: 30956043)
Cell. 1994 Apr 22;77(2):261-71. (PMID: 7513258)
Nature. 1996 Nov 14;384(6605):173-6. (PMID: 8906793)
Biomed Rep. 2017 Dec;7(6):495-503. (PMID: 29188052)
Proc Natl Acad Sci U S A. 2006 Nov 21;103(47):17783-8. (PMID: 17095602)
Cell. 2009 Jun 26;137(7):1293-307. (PMID: 19563760)
Protein Sci. 2022 Oct;31(10):e4411. (PMID: 36173161)
Cell. 1986 Jun 20;45(6):895-904. (PMID: 2423252)
Genome Biol. 2023 Feb 24;24(1):36. (PMID: 36829241)
Nat Commun. 2015 Mar 11;6:6406. (PMID: 25758790)
Oncogene. 2021 Jun;40(24):4061-4078. (PMID: 34031544)
J Biol Chem. 2017 Sep 22;292(38):15705-15716. (PMID: 28724631)
Biochem J. 2023 Aug 16;480(15):1165-1182. (PMID: 37459121)
Proc Natl Acad Sci U S A. 2008 Sep 23;105(38):14377-82. (PMID: 18787129)
Oncogene. 2007 Nov 8;26(51):7213-21. (PMID: 17533376)
Annu Rev Biochem. 2011;80:769-95. (PMID: 21548788)
Cancer Res. 2017 Aug 15;77(16):4498-4505. (PMID: 28522754)
Nat Rev Cancer. 2018 Jun;18(6):341-358. (PMID: 29674709)
Cell. 2010 Jun 25;141(7):1117-34. (PMID: 20602996)
Transl Cancer Res. 2022 Aug;11(8):2931-2935. (PMID: 36093550)
Cancer Cell. 2014 Sep 8;26(3):402-413. (PMID: 25155755)
Proteins. 2003 Feb 15;50(3):437-50. (PMID: 12557186)
Cell. 2001 Sep 21;106(6):745-57. (PMID: 11572780)
J Biol Chem. 2003 Aug 1;278(31):29352-8. (PMID: 12746450)
Proc Natl Acad Sci U S A. 1988 Dec;85(23):9312-6. (PMID: 3143116)
Oncogene. 2018 Jun;37(24):3200-3215. (PMID: 29551767)
Nat Chem Biol. 2020 Mar;16(3):267-277. (PMID: 31959966)
Curr Opin Oncol. 2007 Jan;19(1):55-60. (PMID: 17133113)
Oncogene. 1999 Jul 22;18(29):4275-81. (PMID: 10435641)
Sci Rep. 2015 Mar 17;5:9198. (PMID: 25779975)
Proc Natl Acad Sci U S A. 2014 Oct 28;111(43):E4623-31. (PMID: 25319261)
Bioinformatics. 2006 Nov 1;22(21):2695-6. (PMID: 16940322)
Mol Cell. 2004 Jan 30;13(2):169-78. (PMID: 14759363)
Nat Rev Mol Cell Biol. 2010 Dec;11(12):834-48. (PMID: 21102609)
Proc Natl Acad Sci U S A. 2003 Oct 28;100(22):12654-9. (PMID: 14559966)
Proc Natl Acad Sci U S A. 1998 Nov 24;95(24):14379-83. (PMID: 9826708)
Mol Oncol. 2023 Nov;17(11):2257-2274. (PMID: 36799689)
EMBO J. 2006 Oct 4;25(19):4686-96. (PMID: 16977320)
Nature. 2002 Mar 14;416(6877):187-90. (PMID: 11894096)
Structure. 2002 Sep;10(9):1187-96. (PMID: 12220490)
Oncogene. 1994 Jan;9(1):49-57. (PMID: 8302603)
IUBMB Life. 2020 Jun;72(6):1189-1202. (PMID: 32101380)
Lung Cancer. 2023 Apr;178:66-74. (PMID: 36806896)
Proc Natl Acad Sci U S A. 2014 Dec 30;111(52):18590-5. (PMID: 25518860)
Cancer Discov. 2012 May;2(5):401-4. (PMID: 22588877)
J Biol Chem. 2003 Jul 11;278(28):26007-14. (PMID: 12707268)
Mol Cell Biol. 2005 Nov;25(21):9632-45. (PMID: 16227611)
Nat Struct Mol Biol. 2020 Jan;27(1):92-104. (PMID: 31925410)
Bioinformatics. 2016 Oct 1;32(19):3047-8. (PMID: 27312411)
Proc Natl Acad Sci U S A. 2019 Apr 2;116(14):6818-6827. (PMID: 30867294)
Nat Commun. 2022 Apr 6;13(1):1874. (PMID: 35387990)
Cancer Res. 2003 Oct 1;63(19):6272-81. (PMID: 14559814)
Proc Natl Acad Sci U S A. 2003 Oct 14;100(21):12039-44. (PMID: 14528000)
Cell Rep. 2016 Oct 18;17(4):1171-1183. (PMID: 27760319)
Biochem Soc Trans. 2021 Apr 30;49(2):645-661. (PMID: 33860789)
Cell. 2002 May 3;109(3):275-82. (PMID: 12015977)
Nat Rev Mol Cell Biol. 2004 Jun;5(6):464-71. (PMID: 15173825)
Mol Cell. 2007 Sep 7;27(5):717-30. (PMID: 17803937)
Mol Cell. 2001 Nov;8(5):995-1004. (PMID: 11741535)
Proc Natl Acad Sci U S A. 2006 Mar 7;103(10):3563-8. (PMID: 16537444)
J Transl Med. 2023 Feb 25;21(1):150. (PMID: 36829199)
Bioinformatics. 2009 May 1;25(9):1189-91. (PMID: 19151095)
Leukemia. 2017 May;31(5):1096-1107. (PMID: 27890928)
Cell Chem Biol. 2018 Jul 19;25(7):916-924.e2. (PMID: 29861272)
Mol Cell Biol. 2015 Jan;35(1):264-76. (PMID: 25348715)
Nat Struct Mol Biol. 2008 Oct;15(10):1109-18. (PMID: 18794843)
J Biol Chem. 1991 Oct 15;266(29):19558-64. (PMID: 1655790)
Nat Methods. 2014 Aug;11(8):801-7. (PMID: 25075907)
PLoS Biol. 2013 Oct;11(10):e1001680. (PMID: 24143133)
Cell Chem Biol. 2024 Feb 15;31(2):207-220.e11. (PMID: 37683649)
Trends Biochem Sci. 2011 Feb;36(2):65-77. (PMID: 20971646)
F1000Res. 2021 Jan 18;10:33. (PMID: 34035898)
Genome Biol. 2017 Aug 7;18(1):150. (PMID: 28784151)
Proc Natl Acad Sci U S A. 2006 Feb 28;103(9):3153-8. (PMID: 16492761)
Ann Transl Med. 2015 Apr;3(6):82. (PMID: 25992381)
Cancer Sci. 2022 Mar;113(3):815-827. (PMID: 34997674)
Cancer Discov. 2015 Aug;5(8):850-9. (PMID: 25971938)
Oncogene. 2021 Jun;40(24):4079-4093. (PMID: 34079087)
Sci Signal. 2013 Apr 02;6(269):pl1. (PMID: 23550210)
Mol Cell Biol. 1993 Nov;13(11):6711-22. (PMID: 8413267)
Ann Transl Med. 2017 May;5(10):205. (PMID: 28603720)
J Thorac Oncol. 2019 Oct;14(10):1753-1765. (PMID: 31279006)
Cancer Res. 2006 Jan 1;66(1):283-9. (PMID: 16397241)
Nat Rev Mol Cell Biol. 2003 Dec;4(12):915-25. (PMID: 14685170)
Nature. 1984 Sep 6-11;311(5981):29-33. (PMID: 6590967)
Proc Natl Acad Sci U S A. 2006 Mar 14;103(11):4046-51. (PMID: 16537482)
Mol Cell Biol. 1991 Apr;11(4):1793-803. (PMID: 2005882)
معلومات مُعتمدة: F32 GM152977 United States GM NIGMS NIH HHS; R01 CA239604 United States CA NCI NIH HHS; S10 OD028511 United States OD NIH HHS
تواريخ الأحداث: Date Created: 20230814 Latest Revision: 20240709
رمز التحديث: 20240709
مُعرف محوري في PubMed: PMC10418267
DOI: 10.1101/2023.08.03.551866
PMID: 37577651
قاعدة البيانات: MEDLINE
الوصف
تدمد:2692-8205
DOI:10.1101/2023.08.03.551866