دورية أكاديمية
Unique ligand and kinase-independent roles of the insulin receptor in regulation of cell cycle, senescence and apoptosis.
العنوان: | Unique ligand and kinase-independent roles of the insulin receptor in regulation of cell cycle, senescence and apoptosis. |
---|---|
المؤلفون: | Nagao H; Section of Integrative Physiology and Metabolism, Joslin Diabetes Center, Harvard Medical School, Boston, MA, 02215, USA., Jayavelu AK; Department of Proteomics and Signal Transduction, Max Planck Institute of Biochemistry, 82152, Martinsried, Germany.; Proteomics and Cancer Cell Signaling Group, Clinical Cooperation Unit Pediatric Leukemia, German Cancer Research Center (DKFZ), Heidelberg, Germany., Cai W; Section of Integrative Physiology and Metabolism, Joslin Diabetes Center, Harvard Medical School, Boston, MA, 02215, USA.; Department of Biomedical Sciences, New York Institute of Technology College of Osteopathic Medicine, Old Westbury, NY, 11568, USA., Pan H; Bioinformatics and Biostatistics Core, Joslin Diabetes Center, Harvard Medical School, Boston, MA, 02215, USA., Dreyfuss JM; Bioinformatics and Biostatistics Core, Joslin Diabetes Center, Harvard Medical School, Boston, MA, 02215, USA., Batista TM; Section of Integrative Physiology and Metabolism, Joslin Diabetes Center, Harvard Medical School, Boston, MA, 02215, USA., Brandão BB; Section of Integrative Physiology and Metabolism, Joslin Diabetes Center, Harvard Medical School, Boston, MA, 02215, USA., Mann M; Department of Proteomics and Signal Transduction, Max Planck Institute of Biochemistry, 82152, Martinsried, Germany., Kahn CR; Section of Integrative Physiology and Metabolism, Joslin Diabetes Center, Harvard Medical School, Boston, MA, 02215, USA. c.ronald.kahn@joslin.harvard.edu. |
المصدر: | Nature communications [Nat Commun] 2023 Jan 04; Vol. 14 (1), pp. 57. Date of Electronic Publication: 2023 Jan 04. |
نوع المنشور: | Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't |
اللغة: | English |
بيانات الدورية: | Publisher: Nature Pub. Group Country of Publication: England NLM ID: 101528555 Publication Model: Electronic Cited Medium: Internet ISSN: 2041-1723 (Electronic) Linking ISSN: 20411723 NLM ISO Abbreviation: Nat Commun Subsets: MEDLINE |
أسماء مطبوعة: | Original Publication: [London] : Nature Pub. Group |
مواضيع طبية MeSH: | Apoptosis*/genetics , Cell Division*/genetics , Protein-Tyrosine Kinases*/metabolism , Receptor, Insulin*/genetics , Receptor, Insulin*/metabolism , Cellular Senescence*/genetics, Insulin/metabolism ; Ligands ; Phosphorylation ; Humans ; Animals ; Mice |
مستخلص: | Insulin acts through the insulin receptor (IR) tyrosine kinase to exert its classical metabolic and mitogenic actions. Here, using receptors with either short or long deletion of the β-subunit or mutation of the kinase active site (K1030R), we have uncovered a second, previously unrecognized IR signaling pathway that is intracellular domain-dependent, but ligand and tyrosine kinase-independent (LYK-I). These LYK-I actions of the IR are linked to changes in phosphorylation of a network of proteins involved in the regulation of extracellular matrix organization, cell cycle, ATM signaling and cellular senescence; and result in upregulation of expression of multiple extracellular matrix-related genes and proteins, down-regulation of immune/interferon-related genes and proteins, and increased sensitivity to apoptosis. Thus, in addition to classical ligand and tyrosine kinase-dependent (LYK-D) signaling, the IR regulates a second, ligand and tyrosine kinase-independent (LYK-I) pathway, which regulates the cellular machinery involved in senescence, matrix interaction and response to extrinsic challenges. (© 2023. The Author(s).) |
References: | Mol Metab. 2021 Oct;52:101304. (PMID: 34274528) Nature. 2010 Sep 2;467(7311):59-63. (PMID: 20811452) Nature. 2018 Apr 5;556(7699):122-125. (PMID: 29512653) Nature. 2011 May 19;473(7347):337-42. (PMID: 21593866) J Biol Chem. 2010 May 28;285(22):17235-45. (PMID: 20360006) Mol Endocrinol. 2005 Mar;19(3):771-80. (PMID: 15591537) Cell. 2019 Apr 18;177(3):722-736.e22. (PMID: 30955890) Proc Natl Acad Sci U S A. 2020 Mar 24;117(12):6733-6740. (PMID: 32156724) Cell Res. 2019 Jul;29(7):509-511. (PMID: 31160720) Cold Spring Harb Perspect Biol. 2014 Jan 01;6(1):. (PMID: 24384568) Cell. 2017 Jun 1;169(6):1000-1011. (PMID: 28575665) Nat Commun. 2019 Apr 5;10(1):1582. (PMID: 30952843) Endocr Rev. 2022 Mar 9;43(2):314-328. (PMID: 34490882) Mol Cancer Ther. 2016 Aug;15(8):1781-91. (PMID: 27413114) Nucleic Acids Res. 2015 Jan;43(Database issue):D531-5. (PMID: 25332398) Nat Protoc. 2018 Sep;13(9):1897-1916. (PMID: 30190555) Endocr Rev. 2017 Oct 1;38(5):379-431. (PMID: 28973479) PLoS One. 2009 Jun 19;4(6):e5985. (PMID: 19543529) EMBO J. 2013 Oct 16;32(20):2751-63. (PMID: 24065129) Nucleic Acids Res. 2015 Jan;43(Database issue):D512-20. (PMID: 25514926) Proc Natl Acad Sci U S A. 2021 Apr 27;118(17):. (PMID: 33879610) Cell Signal. 2004 Aug;16(8):873-80. (PMID: 15157666) Bioinformatics. 2011 Jun 15;27(12):1739-40. (PMID: 21546393) J Biol Chem. 1994 Apr 8;269(14):10604-8. (PMID: 8144649) Nat Biotechnol. 2016 May;34(5):525-7. (PMID: 27043002) Front Endocrinol (Lausanne). 2013 Jun 12;4:71. (PMID: 23781214) Trends Endocrinol Metab. 2021 Sep;32(9):721-730. (PMID: 34266706) Nucleic Acids Res. 2015 Apr 20;43(7):e47. (PMID: 25605792) J Clin Invest. 2021 Jan 4;131(1):. (PMID: 33393497) Bioinformatics. 2018 Sep 1;34(17):i884-i890. (PMID: 30423086) Genome Biol. 2010;11(3):R25. (PMID: 20196867) F1000Res. 2015 Dec 30;4:1521. (PMID: 26925227) Genes Dev. 2020 Dec 1;34(23-24):1565-1576. (PMID: 33262144) Annu Rev Physiol. 2007;69:561-77. (PMID: 17002595) Cell Metab. 2009 Mar;9(3):213-4. (PMID: 19254565) NPJ Aging Mech Dis. 2018 Nov 15;4:11. (PMID: 30455980) N Engl J Med. 2009 Oct 15;361(16):1570-83. (PMID: 19828534) Int J Mol Sci. 2018 May 08;19(5):. (PMID: 29738498) Nat Commun. 2017 Mar 27;8:14892. (PMID: 28345670) Nat Cell Biol. 2017 Sep;19(9):1061-1070. (PMID: 28759028) Sci Signal. 2010 Dec 07;3(151):ra87. (PMID: 21139139) Proc Natl Acad Sci U S A. 2006 Jun 13;103(24):9220-5. (PMID: 16751281) Biochim Biophys Acta. 2011 Jan;1813(1):238-59. (PMID: 20969895) Nucleic Acids Res. 2019 Jan 8;47(D1):D607-D613. (PMID: 30476243) J Biochem. 2021 Mar 5;169(2):147-153. (PMID: 33002139) Front Oncol. 2013 Jul 04;3:171. (PMID: 23847762) NPJ Breast Cancer. 2019 Jul 26;5:22. (PMID: 31372497) Diabetes. 2012 Sep;61(9):2289-98. (PMID: 22751693) J Biol Chem. 1989 Aug 5;264(22):12820-5. (PMID: 2753889) Bioinformatics. 2008 Mar 1;24(5):719-20. (PMID: 18024473) Nat Commun. 2016 Jan 04;7:10060. (PMID: 26725982) Front Pharmacol. 2014 May 27;5:123. (PMID: 24904424) Cell Biosci. 2012 Jul 09;2(1):24. (PMID: 22769588) J Biol Chem. 2016 Nov 11;291(46):24261-24279. (PMID: 27646004) Aging Cell. 2020 Oct;19(10):e13234. (PMID: 32918364) Biochim Biophys Acta. 2007 Jan;1775(1):163-80. (PMID: 17084981) Cell Biochem Funct. 2011 Oct;29(7):589-96. (PMID: 21830225) Science. 2009 Nov 27;326(5957):1216-9. (PMID: 19965464) Endocr Rev. 2021 Sep 28;42(5):503-527. (PMID: 34273145) Proc Natl Acad Sci U S A. 2014 Oct 7;111(40):14512-7. (PMID: 25246545) Nat Immunol. 2019 Dec;20(12):1574-1583. (PMID: 31745335) Bioinformatics. 2009 Mar 15;25(6):765-71. (PMID: 19176553) Nat Med. 2017 Jul 11;23(7):804-814. (PMID: 28697184) J Virol. 2016 Jun 10;90(13):5850-5854. (PMID: 27053550) Cell Metab. 2020 Nov 3;32(5):844-859.e5. (PMID: 32888406) Mol Metab. 2019 Apr;22:21-36. (PMID: 30795914) Nature. 2019 Apr;568(7752):344-350. (PMID: 30944469) Biochem J. 2001 Mar 1;354(Pt 2):315-22. (PMID: 11171109) Nucleic Acids Res. 2011 Jan;39(Database issue):D777-87. (PMID: 21037261) Database (Oxford). 2016 Jul 03;2016:. (PMID: 27374120) Front Cell Dev Biol. 2021 May 26;9:688388. (PMID: 34124074) Bioinformatics. 2003 Jan 22;19(2):185-93. (PMID: 12538238) Nat Rev Mol Cell Biol. 2019 Mar;20(3):175-193. (PMID: 30655609) Nat Commun. 2021 Nov 29;12(1):6951. (PMID: 34845204) Diabetologia. 2021 May;64(5):994-1006. (PMID: 33730188) J Clin Invest. 2018 Apr 2;128(4):1238-1246. (PMID: 29608137) |
معلومات مُعتمدة: | K01 DK120740 United States DK NIDDK NIH HHS; P30 DK036836 United States DK NIDDK NIH HHS; R01 DK128429 United States DK NIDDK NIH HHS; P30 DK057521 United States DK NIDDK NIH HHS; R01 DK031036 United States DK NIDDK NIH HHS |
المشرفين على المادة: | 0 (Insulin) 0 (Ligands) EC 2.7.10.1 (Protein-Tyrosine Kinases) EC 2.7.10.1 (Receptor, Insulin) |
تواريخ الأحداث: | Date Created: 20230104 Date Completed: 20230123 Latest Revision: 20230306 |
رمز التحديث: | 20240628 |
مُعرف محوري في PubMed: | PMC9812992 |
DOI: | 10.1038/s41467-022-35693-5 |
PMID: | 36599833 |
قاعدة البيانات: | MEDLINE |
تدمد: | 2041-1723 |
---|---|
DOI: | 10.1038/s41467-022-35693-5 |