Unique ligand and kinase-independent roles of the insulin receptor in regulation of cell cycle, senescence and apoptosis

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Unique ligand and kinase-independent roles of the insulin receptor in regulation of cell cycle, senescence and apoptosis. / Nagao, Hirofumi; Jayavelu, Ashok Kumar; Cai, Weikang; Pan, Hui; Dreyfuss, Jonathan M; Batista, Thiago M; Brandão, Bruna B; Mann, Matthias; Kahn, C Ronald.

In: Nature Communications, Vol. 14, No. 1, 04.01.2023, p. 57.

Research output: Contribution to journal › Journal article › Research › peer-review

Harvard

Nagao, H, Jayavelu, AK, Cai, W, Pan, H, Dreyfuss, JM, Batista, TM, Brandão, BB, Mann, M & Kahn, CR 2023, 'Unique ligand and kinase-independent roles of the insulin receptor in regulation of cell cycle, senescence and apoptosis', Nature Communications, vol. 14, no. 1, pp. 57. https://doi.org/10.1038/s41467-022-35693-5

APA

Nagao, H., Jayavelu, A. K., Cai, W., Pan, H., Dreyfuss, J. M., Batista, T. M., Brandão, B. B., Mann, M., & Kahn, C. R. (2023). Unique ligand and kinase-independent roles of the insulin receptor in regulation of cell cycle, senescence and apoptosis. Nature Communications, 14(1), 57. https://doi.org/10.1038/s41467-022-35693-5

Vancouver

Nagao H, Jayavelu AK, Cai W, Pan H, Dreyfuss JM, Batista TM et al. Unique ligand and kinase-independent roles of the insulin receptor in regulation of cell cycle, senescence and apoptosis. Nature Communications. 2023 Jan 4;14(1):57. https://doi.org/10.1038/s41467-022-35693-5

Author

Nagao, Hirofumi ; Jayavelu, Ashok Kumar ; Cai, Weikang ; Pan, Hui ; Dreyfuss, Jonathan M ; Batista, Thiago M ; Brandão, Bruna B ; Mann, Matthias ; Kahn, C Ronald. / Unique ligand and kinase-independent roles of the insulin receptor in regulation of cell cycle, senescence and apoptosis. In: Nature Communications. 2023 ; Vol. 14, No. 1. pp. 57.

Bibtex

@article{195e266370d64e30a1b8ad02e434720a,
title = "Unique ligand and kinase-independent roles of the insulin receptor in regulation of cell cycle, senescence and apoptosis",
abstract = "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.",
keywords = "Apoptosis/genetics, Cell Division/genetics, Insulin/metabolism, Ligands, Phosphorylation, Protein-Tyrosine Kinases/metabolism, Receptor, Insulin/genetics, Cellular Senescence/genetics, Humans, Animals, Mice",
author = "Hirofumi Nagao and Jayavelu, {Ashok Kumar} and Weikang Cai and Hui Pan and Dreyfuss, {Jonathan M} and Batista, {Thiago M} and Brand{\~a}o, {Bruna B} and Matthias Mann and Kahn, {C Ronald}",
note = "{\textcopyright} 2023. The Author(s).",
year = "2023",
month = jan,
day = "4",
doi = "10.1038/s41467-022-35693-5",
language = "English",
volume = "14",
pages = "57",
journal = "Nature Communications",
issn = "2041-1723",
publisher = "nature publishing group",
number = "1",

}

RIS

TY - JOUR

T1 - Unique ligand and kinase-independent roles of the insulin receptor in regulation of cell cycle, senescence and apoptosis

AU - Nagao, Hirofumi

AU - Jayavelu, Ashok Kumar

AU - Cai, Weikang

AU - Pan, Hui

AU - Dreyfuss, Jonathan M

AU - Batista, Thiago M

AU - Brandão, Bruna B

AU - Mann, Matthias

AU - Kahn, C Ronald

N1 - © 2023. The Author(s).

PY - 2023/1/4

Y1 - 2023/1/4

N2 - 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.

AB - 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.

KW - Apoptosis/genetics

KW - Cell Division/genetics

KW - Insulin/metabolism

KW - Ligands

KW - Phosphorylation

KW - Protein-Tyrosine Kinases/metabolism

KW - Receptor, Insulin/genetics

KW - Cellular Senescence/genetics

KW - Humans

KW - Animals

KW - Mice

U2 - 10.1038/s41467-022-35693-5

DO - 10.1038/s41467-022-35693-5

M3 - Journal article

C2 - 36599833

VL - 14

SP - 57

JO - Nature Communications

JF - Nature Communications

SN - 2041-1723

IS - 1

ER -

ID: 346585564