Tyrosine Phosphorylation of Mitochondrial Creatine Kinase 1 Enhances a Druggable Tumor Energy Shuttle Pathway

Kiran Kurmi; Sadae Hitosugi; Jia Yu; Felix Boakye-Agyeman; Elizabeth K. Wiese; Thomas R. Larson; Qing Dai; Yuichi J. Machida; Zhenkun Lou; Liewei Wang; Judy C. Boughey; Scott H. Kaufmann; Matthew P. Goetz; Larry M. Karnitz; Taro Hitosugi

doi:10.1016/j.cmet.2018.08.008

Tyrosine Phosphorylation of Mitochondrial Creatine Kinase 1 Enhances a Druggable Tumor Energy Shuttle Pathway

Kiran Kurmi, Sadae Hitosugi, Jia Yu, Felix Boakye-Agyeman, Elizabeth K. Wiese, Thomas R. Larson, Qing Dai, Yuichi J. Machida, Zhenkun Lou, Liewei Wang, Judy C. Boughey, Scott H. Kaufmann, Matthew P. Goetz, Larry M. Karnitz, Taro Hitosugi

Research output: Contribution to journal › Article › peer-review

14 Scopus citations

Abstract

Kurmi et al. report that the phosphocreatine (PCr) energy shuttle is important for breast tumor metabolism and growth. This energy shuttle is activated through MtCK1 Y153 phosphorylation by the HER2/ABL signaling axis. Using a creatine analog cyclocreatine that inhibits the PCr energy shuttle, they demonstrate reduced growth of trastuzumab-resistant breast tumors in mice.

Original language	English (US)
Pages (from-to)	833-847.e8
Journal	Cell Metabolism
Volume	28
Issue number	6
DOIs	https://doi.org/10.1016/j.cmet.2018.08.008
State	Published - Dec 4 2018

Keywords

ABL kinase
HER2 tyrosine kinase
breast cancer
cyclocreatine
mitochondria
mitochondrial bioenergetics
mitochondrial creatine kinase
oncogenic tyrosine kinase
phosphocreatine
tyrosine phosphorylation

ASJC Scopus subject areas

Physiology
Molecular Biology
Cell Biology

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10.1016/j.cmet.2018.08.008

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Kurmi, K., Hitosugi, S., Yu, J., Boakye-Agyeman, F., Wiese, E. K., Larson, T. R., Dai, Q., Machida, Y. J., Lou, Z., Wang, L., Boughey, J. C., Kaufmann, S. H., Goetz, M. P., Karnitz, L. M., & Hitosugi, T. (2018). Tyrosine Phosphorylation of Mitochondrial Creatine Kinase 1 Enhances a Druggable Tumor Energy Shuttle Pathway. Cell Metabolism, 28(6), 833-847.e8. https://doi.org/10.1016/j.cmet.2018.08.008

Kurmi, K, Hitosugi, S, Yu, J, Boakye-Agyeman, F, Wiese, EK, Larson, TR, Dai, Q, Machida, YJ, Lou, Z , Wang, L , Boughey, JC , Kaufmann, SH , Goetz, MP , Karnitz, LM & Hitosugi, T 2018, 'Tyrosine Phosphorylation of Mitochondrial Creatine Kinase 1 Enhances a Druggable Tumor Energy Shuttle Pathway', Cell Metabolism, vol. 28, no. 6, pp. 833-847.e8. https://doi.org/10.1016/j.cmet.2018.08.008

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title = "Tyrosine Phosphorylation of Mitochondrial Creatine Kinase 1 Enhances a Druggable Tumor Energy Shuttle Pathway",

abstract = "Kurmi et al. report that the phosphocreatine (PCr) energy shuttle is important for breast tumor metabolism and growth. This energy shuttle is activated through MtCK1 Y153 phosphorylation by the HER2/ABL signaling axis. Using a creatine analog cyclocreatine that inhibits the PCr energy shuttle, they demonstrate reduced growth of trastuzumab-resistant breast tumors in mice.",

keywords = "ABL kinase, HER2 tyrosine kinase, breast cancer, cyclocreatine, mitochondria, mitochondrial bioenergetics, mitochondrial creatine kinase, oncogenic tyrosine kinase, phosphocreatine, tyrosine phosphorylation",

author = "Kiran Kurmi and Sadae Hitosugi and Jia Yu and Felix Boakye-Agyeman and Wiese, {Elizabeth K.} and Larson, {Thomas R.} and Qing Dai and Machida, {Yuichi J.} and Zhenkun Lou and Liewei Wang and Boughey, {Judy C.} and Kaufmann, {Scott H.} and Goetz, {Matthew P.} and Karnitz, {Larry M.} and Taro Hitosugi",

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doi = "10.1016/j.cmet.2018.08.008",

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AU - Kurmi, Kiran

AU - Hitosugi, Sadae

AU - Yu, Jia

AU - Boakye-Agyeman, Felix

AU - Wiese, Elizabeth K.

AU - Larson, Thomas R.

AU - Dai, Qing

AU - Machida, Yuichi J.

AU - Lou, Zhenkun

AU - Wang, Liewei

AU - Boughey, Judy C.

AU - Kaufmann, Scott H.

AU - Goetz, Matthew P.

AU - Karnitz, Larry M.

AU - Hitosugi, Taro

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AB - Kurmi et al. report that the phosphocreatine (PCr) energy shuttle is important for breast tumor metabolism and growth. This energy shuttle is activated through MtCK1 Y153 phosphorylation by the HER2/ABL signaling axis. Using a creatine analog cyclocreatine that inhibits the PCr energy shuttle, they demonstrate reduced growth of trastuzumab-resistant breast tumors in mice.

KW - ABL kinase

KW - HER2 tyrosine kinase

KW - breast cancer

KW - cyclocreatine

KW - mitochondria

KW - mitochondrial bioenergetics

KW - mitochondrial creatine kinase

KW - oncogenic tyrosine kinase

KW - phosphocreatine

KW - tyrosine phosphorylation

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Tyrosine Phosphorylation of Mitochondrial Creatine Kinase 1 Enhances a Druggable Tumor Energy Shuttle Pathway

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Keywords

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