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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 uncover a second novel 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, novel ligand and tyrosine kinase-independent (LYK-I) pathway which regulates the cellular machinery involved in senescence, matrix interaction and response to extrinsic challenges.

ORGANISM(S): Mus musculus

PROVIDER: GSE206565 | GEO | 2022/11/25

REPOSITORIES: GEO

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Unique Ligand and Kinase-Independent Roles of the Insulin Receptor in Regulation of Cell Cycle, Senescence and Apoptosis

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