Distinct signaling by insulin and IGF-1 receptors and their extra- and intracellular domains

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Distinct signaling by insulin and IGF-1 receptors and their extra- and intracellular domains. / Nagao, Hirofumi; Cai, Weikang; Wewer Albrechtsen, Nicolai J; Steger, Martin; Batista, Thiago M; Pan, Hui; Dreyfuss, Jonathan M; Mann, Matthias; Kahn, C Ronald.

In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 118, No. 17, e2019474118, 2021.

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

Harvard

Nagao, H, Cai, W, Wewer Albrechtsen, NJ, Steger, M, Batista, TM, Pan, H, Dreyfuss, JM, Mann, M & Kahn, CR 2021, 'Distinct signaling by insulin and IGF-1 receptors and their extra- and intracellular domains', Proceedings of the National Academy of Sciences of the United States of America, vol. 118, no. 17, e2019474118. https://doi.org/10.1073/pnas.2019474118

APA

Nagao, H., Cai, W., Wewer Albrechtsen, N. J., Steger, M., Batista, T. M., Pan, H., Dreyfuss, J. M., Mann, M., & Kahn, C. R. (2021). Distinct signaling by insulin and IGF-1 receptors and their extra- and intracellular domains. Proceedings of the National Academy of Sciences of the United States of America, 118(17), [e2019474118]. https://doi.org/10.1073/pnas.2019474118

Vancouver

Nagao H, Cai W, Wewer Albrechtsen NJ, Steger M, Batista TM, Pan H et al. Distinct signaling by insulin and IGF-1 receptors and their extra- and intracellular domains. Proceedings of the National Academy of Sciences of the United States of America. 2021;118(17). e2019474118. https://doi.org/10.1073/pnas.2019474118

Author

Nagao, Hirofumi ; Cai, Weikang ; Wewer Albrechtsen, Nicolai J ; Steger, Martin ; Batista, Thiago M ; Pan, Hui ; Dreyfuss, Jonathan M ; Mann, Matthias ; Kahn, C Ronald. / Distinct signaling by insulin and IGF-1 receptors and their extra- and intracellular domains. In: Proceedings of the National Academy of Sciences of the United States of America. 2021 ; Vol. 118, No. 17.

Bibtex

@article{9720eea811f74892bced3c7e6f4b847a,
title = "Distinct signaling by insulin and IGF-1 receptors and their extra- and intracellular domains",
abstract = "Insulin and insulin-like growth factor 1 (IGF-1) receptors share many downstream signaling pathways but have unique biological effects. To define the molecular signals contributing to these distinct activities, we performed global phosphoproteomics on cells expressing either insulin receptor (IR), IGF-1 receptor (IGF1R), or chimeric IR-IGF1R receptors. We show that IR preferentially stimulates phosphorylations associated with mammalian target of rapamycin complex 1 (mTORC1) and Akt pathways, whereas IGF1R preferentially stimulates phosphorylations on proteins associated with the Ras homolog family of guanosine triphosphate hydrolases (Rho GTPases), and cell cycle progression. There were also major differences in the phosphoproteome between cells expressing IR versus IGF1R in the unstimulated state, including phosphorylation of proteins involved in membrane trafficking, chromatin remodeling, and cell cycle. In cells expressing chimeric IR-IGF1R receptors, these differences in signaling could be mapped to contributions of both the extra- and intracellular domains of these receptors. Thus, despite their high homology, IR and IGF1R preferentially regulate distinct networks of phosphorylation in both the basal and stimulated states, allowing for the unique effects of these hormones on organismal function.",
author = "Hirofumi Nagao and Weikang Cai and {Wewer Albrechtsen}, {Nicolai J} and Martin Steger and Batista, {Thiago M} and Hui Pan and Dreyfuss, {Jonathan M} and Matthias Mann and Kahn, {C Ronald}",
year = "2021",
doi = "10.1073/pnas.2019474118",
language = "English",
volume = "118",
journal = "Proceedings of the National Academy of Sciences of the United States of America",
issn = "0027-8424",
publisher = "The National Academy of Sciences of the United States of America",
number = "17",

}

RIS

TY - JOUR

T1 - Distinct signaling by insulin and IGF-1 receptors and their extra- and intracellular domains

AU - Nagao, Hirofumi

AU - Cai, Weikang

AU - Wewer Albrechtsen, Nicolai J

AU - Steger, Martin

AU - Batista, Thiago M

AU - Pan, Hui

AU - Dreyfuss, Jonathan M

AU - Mann, Matthias

AU - Kahn, C Ronald

PY - 2021

Y1 - 2021

N2 - Insulin and insulin-like growth factor 1 (IGF-1) receptors share many downstream signaling pathways but have unique biological effects. To define the molecular signals contributing to these distinct activities, we performed global phosphoproteomics on cells expressing either insulin receptor (IR), IGF-1 receptor (IGF1R), or chimeric IR-IGF1R receptors. We show that IR preferentially stimulates phosphorylations associated with mammalian target of rapamycin complex 1 (mTORC1) and Akt pathways, whereas IGF1R preferentially stimulates phosphorylations on proteins associated with the Ras homolog family of guanosine triphosphate hydrolases (Rho GTPases), and cell cycle progression. There were also major differences in the phosphoproteome between cells expressing IR versus IGF1R in the unstimulated state, including phosphorylation of proteins involved in membrane trafficking, chromatin remodeling, and cell cycle. In cells expressing chimeric IR-IGF1R receptors, these differences in signaling could be mapped to contributions of both the extra- and intracellular domains of these receptors. Thus, despite their high homology, IR and IGF1R preferentially regulate distinct networks of phosphorylation in both the basal and stimulated states, allowing for the unique effects of these hormones on organismal function.

AB - Insulin and insulin-like growth factor 1 (IGF-1) receptors share many downstream signaling pathways but have unique biological effects. To define the molecular signals contributing to these distinct activities, we performed global phosphoproteomics on cells expressing either insulin receptor (IR), IGF-1 receptor (IGF1R), or chimeric IR-IGF1R receptors. We show that IR preferentially stimulates phosphorylations associated with mammalian target of rapamycin complex 1 (mTORC1) and Akt pathways, whereas IGF1R preferentially stimulates phosphorylations on proteins associated with the Ras homolog family of guanosine triphosphate hydrolases (Rho GTPases), and cell cycle progression. There were also major differences in the phosphoproteome between cells expressing IR versus IGF1R in the unstimulated state, including phosphorylation of proteins involved in membrane trafficking, chromatin remodeling, and cell cycle. In cells expressing chimeric IR-IGF1R receptors, these differences in signaling could be mapped to contributions of both the extra- and intracellular domains of these receptors. Thus, despite their high homology, IR and IGF1R preferentially regulate distinct networks of phosphorylation in both the basal and stimulated states, allowing for the unique effects of these hormones on organismal function.

U2 - 10.1073/pnas.2019474118

DO - 10.1073/pnas.2019474118

M3 - Journal article

C2 - 33879610

VL - 118

JO - Proceedings of the National Academy of Sciences of the United States of America

JF - Proceedings of the National Academy of Sciences of the United States of America

SN - 0027-8424

IS - 17

M1 - e2019474118

ER -

ID: 261519139