Global phosphoproteomic analysis of human skeletal muscle reveals a network of exercise-regulated kinases and AMPK substrates

Research output: Contribution to journalJournal articlepeer-review

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Global phosphoproteomic analysis of human skeletal muscle reveals a network of exercise-regulated kinases and AMPK substrates. / Hoffman, Nolan J; Parker, Benjamin L; Chaudhuri, Rima; Fisher-Wellman, Kelsey H.; Kleinert, Maximilian; Humphrey, Sean J; Yang, Pengyi; Holliday, Mira; Trefely, Sophie; Fazakerley, Daniel J; Stöckli, Jacqueline; Burchfield, James G; Jensen, Thomas Elbenhardt; Jothi, Raja; Kiens, Bente; Wojtaszewski, Jørgen; Richter, Erik A.; James, David E.

In: Cell Metabolism, Vol. 22, No. 5, 2015, p. 922-935.

Research output: Contribution to journalJournal articlepeer-review

Harvard

Hoffman, NJ, Parker, BL, Chaudhuri, R, Fisher-Wellman, KH, Kleinert, M, Humphrey, SJ, Yang, P, Holliday, M, Trefely, S, Fazakerley, DJ, Stöckli, J, Burchfield, JG, Jensen, TE, Jothi, R, Kiens, B, Wojtaszewski, J, Richter, EA & James, DE 2015, 'Global phosphoproteomic analysis of human skeletal muscle reveals a network of exercise-regulated kinases and AMPK substrates', Cell Metabolism, vol. 22, no. 5, pp. 922-935. https://doi.org/10.1016/j.cmet.2015.09.001

APA

Hoffman, N. J., Parker, B. L., Chaudhuri, R., Fisher-Wellman, K. H., Kleinert, M., Humphrey, S. J., Yang, P., Holliday, M., Trefely, S., Fazakerley, D. J., Stöckli, J., Burchfield, J. G., Jensen, T. E., Jothi, R., Kiens, B., Wojtaszewski, J., Richter, E. A., & James, D. E. (2015). Global phosphoproteomic analysis of human skeletal muscle reveals a network of exercise-regulated kinases and AMPK substrates. Cell Metabolism, 22(5), 922-935. https://doi.org/10.1016/j.cmet.2015.09.001

Vancouver

Hoffman NJ, Parker BL, Chaudhuri R, Fisher-Wellman KH, Kleinert M, Humphrey SJ et al. Global phosphoproteomic analysis of human skeletal muscle reveals a network of exercise-regulated kinases and AMPK substrates. Cell Metabolism. 2015;22(5):922-935. https://doi.org/10.1016/j.cmet.2015.09.001

Author

Hoffman, Nolan J ; Parker, Benjamin L ; Chaudhuri, Rima ; Fisher-Wellman, Kelsey H. ; Kleinert, Maximilian ; Humphrey, Sean J ; Yang, Pengyi ; Holliday, Mira ; Trefely, Sophie ; Fazakerley, Daniel J ; Stöckli, Jacqueline ; Burchfield, James G ; Jensen, Thomas Elbenhardt ; Jothi, Raja ; Kiens, Bente ; Wojtaszewski, Jørgen ; Richter, Erik A. ; James, David E. / Global phosphoproteomic analysis of human skeletal muscle reveals a network of exercise-regulated kinases and AMPK substrates. In: Cell Metabolism. 2015 ; Vol. 22, No. 5. pp. 922-935.

Bibtex

@article{192c7d0c32c94ce6b9f4ab782f68f70a,
title = "Global phosphoproteomic analysis of human skeletal muscle reveals a network of exercise-regulated kinases and AMPK substrates",
abstract = "Exercise is essential in regulating energy metabolism and whole-body insulin sensitivity. To explore the exercise signaling network, we undertook a globalanalysis of protein phosphorylation in human skeletal muscle biopsies from untrained healthy males before and after a single high-intensity exercise bout, revealing 1,004 unique exercise-regulated phosphosites on 562 proteins. These included substrates of known exercise-regulated kinases (AMPK, PKA, CaMK, MAPK, mTOR), yet the majority of kinases and substrate phosphosites have not previously been implicated in exercise signaling. Given the importance of AMPK in exercise-regulated metabolism, we performed a targeted in vitro AMPK screen and employed machine learning to predict exercise-regulated AMPK substrates. We validated eight predicted AMPK substrates, including AKAP1, using targeted phosphoproteomics. Functional characterization revealed an undescribed role or AMPKdependent phosphorylation of AKAP1 in mitochondrial respiration. These data expose the unexplored complexity of acute exercise signaling and provideinsights into the role of AMPK in mitochondrial biochemistry.",
author = "Hoffman, {Nolan J} and Parker, {Benjamin L} and Rima Chaudhuri and Fisher-Wellman, {Kelsey H.} and Maximilian Kleinert and Humphrey, {Sean J} and Pengyi Yang and Mira Holliday and Sophie Trefely and Fazakerley, {Daniel J} and Jacqueline St{\"o}ckli and Burchfield, {James G} and Jensen, {Thomas Elbenhardt} and Raja Jothi and Bente Kiens and J{\o}rgen Wojtaszewski and Richter, {Erik A.} and James, {David E}",
note = "CURIS 2015 NEXS 351",
year = "2015",
doi = "10.1016/j.cmet.2015.09.001",
language = "English",
volume = "22",
pages = "922--935",
journal = "Cell Metabolism",
issn = "1550-4131",
publisher = "Cell Press",
number = "5",

}

RIS

TY - JOUR

T1 - Global phosphoproteomic analysis of human skeletal muscle reveals a network of exercise-regulated kinases and AMPK substrates

AU - Hoffman, Nolan J

AU - Parker, Benjamin L

AU - Chaudhuri, Rima

AU - Fisher-Wellman, Kelsey H.

AU - Kleinert, Maximilian

AU - Humphrey, Sean J

AU - Yang, Pengyi

AU - Holliday, Mira

AU - Trefely, Sophie

AU - Fazakerley, Daniel J

AU - Stöckli, Jacqueline

AU - Burchfield, James G

AU - Jensen, Thomas Elbenhardt

AU - Jothi, Raja

AU - Kiens, Bente

AU - Wojtaszewski, Jørgen

AU - Richter, Erik A.

AU - James, David E

N1 - CURIS 2015 NEXS 351

PY - 2015

Y1 - 2015

N2 - Exercise is essential in regulating energy metabolism and whole-body insulin sensitivity. To explore the exercise signaling network, we undertook a globalanalysis of protein phosphorylation in human skeletal muscle biopsies from untrained healthy males before and after a single high-intensity exercise bout, revealing 1,004 unique exercise-regulated phosphosites on 562 proteins. These included substrates of known exercise-regulated kinases (AMPK, PKA, CaMK, MAPK, mTOR), yet the majority of kinases and substrate phosphosites have not previously been implicated in exercise signaling. Given the importance of AMPK in exercise-regulated metabolism, we performed a targeted in vitro AMPK screen and employed machine learning to predict exercise-regulated AMPK substrates. We validated eight predicted AMPK substrates, including AKAP1, using targeted phosphoproteomics. Functional characterization revealed an undescribed role or AMPKdependent phosphorylation of AKAP1 in mitochondrial respiration. These data expose the unexplored complexity of acute exercise signaling and provideinsights into the role of AMPK in mitochondrial biochemistry.

AB - Exercise is essential in regulating energy metabolism and whole-body insulin sensitivity. To explore the exercise signaling network, we undertook a globalanalysis of protein phosphorylation in human skeletal muscle biopsies from untrained healthy males before and after a single high-intensity exercise bout, revealing 1,004 unique exercise-regulated phosphosites on 562 proteins. These included substrates of known exercise-regulated kinases (AMPK, PKA, CaMK, MAPK, mTOR), yet the majority of kinases and substrate phosphosites have not previously been implicated in exercise signaling. Given the importance of AMPK in exercise-regulated metabolism, we performed a targeted in vitro AMPK screen and employed machine learning to predict exercise-regulated AMPK substrates. We validated eight predicted AMPK substrates, including AKAP1, using targeted phosphoproteomics. Functional characterization revealed an undescribed role or AMPKdependent phosphorylation of AKAP1 in mitochondrial respiration. These data expose the unexplored complexity of acute exercise signaling and provideinsights into the role of AMPK in mitochondrial biochemistry.

U2 - 10.1016/j.cmet.2015.09.001

DO - 10.1016/j.cmet.2015.09.001

M3 - Journal article

C2 - 26437602

VL - 22

SP - 922

EP - 935

JO - Cell Metabolism

JF - Cell Metabolism

SN - 1550-4131

IS - 5

ER -

ID: 144931326