Nature Communications (Jan 2019)
Tyrosyl phosphorylation of KRAS stalls GTPase cycle via alteration of switch I and II conformation
- Yoshihito Kano,
- Teklab Gebregiworgis,
- Christopher B. Marshall,
- Nikolina Radulovich,
- Betty P. K. Poon,
- Jonathan St-Germain,
- Jonathan D. Cook,
- Ivette Valencia-Sama,
- Benjamin M. M. Grant,
- Silvia Gabriela Herrera,
- Jinmin Miao,
- Brian Raught,
- Meredith S. Irwin,
- Jeffrey E. Lee,
- Jen Jen Yeh,
- Zhong-Yin Zhang,
- Ming-Sound Tsao,
- Mitsuhiko Ikura,
- Michael Ohh
Affiliations
- Yoshihito Kano
- Department of Laboratory Medicine and Pathobiology, University of Toronto
- Teklab Gebregiworgis
- Princess Margaret Cancer Centre, University Health Network and Department of Medical Biophysics, University of Toronto
- Christopher B. Marshall
- Princess Margaret Cancer Centre, University Health Network and Department of Medical Biophysics, University of Toronto
- Nikolina Radulovich
- Princess Margaret Cancer Centre, University Health Network and Department of Pathology, University of Toronto
- Betty P. K. Poon
- Department of Laboratory Medicine and Pathobiology, University of Toronto
- Jonathan St-Germain
- Princess Margaret Cancer Centre, University Health Network and Department of Medical Biophysics, University of Toronto
- Jonathan D. Cook
- Department of Laboratory Medicine and Pathobiology, University of Toronto
- Ivette Valencia-Sama
- Department of Laboratory Medicine and Pathobiology, University of Toronto
- Benjamin M. M. Grant
- Princess Margaret Cancer Centre, University Health Network and Department of Medical Biophysics, University of Toronto
- Silvia Gabriela Herrera
- Lineberger Comprehensive Cancer Center, University of North Carolina
- Jinmin Miao
- Department of Medicinal Chemistry and Molecular Pharmacology, Center for Cancer Research and Institute for Drug Discovery, Purdue University
- Brian Raught
- Princess Margaret Cancer Centre, University Health Network and Department of Medical Biophysics, University of Toronto
- Meredith S. Irwin
- Peter Gilgan Centre for Research and Learning, The Hospital for Sick Children
- Jeffrey E. Lee
- Department of Laboratory Medicine and Pathobiology, University of Toronto
- Jen Jen Yeh
- Lineberger Comprehensive Cancer Center, University of North Carolina
- Zhong-Yin Zhang
- Department of Medicinal Chemistry and Molecular Pharmacology, Center for Cancer Research and Institute for Drug Discovery, Purdue University
- Ming-Sound Tsao
- Princess Margaret Cancer Centre, University Health Network and Department of Pathology, University of Toronto
- Mitsuhiko Ikura
- Princess Margaret Cancer Centre, University Health Network and Department of Medical Biophysics, University of Toronto
- Michael Ohh
- Department of Laboratory Medicine and Pathobiology, University of Toronto
- DOI
- https://doi.org/10.1038/s41467-018-08115-8
- Journal volume & issue
-
Vol. 10,
no. 1
pp. 1 – 14
Abstract
Deregulation of the RAS GTPase cycle due to mutations in RAS genes is commonly associated with cancer development. Here authors use NMR and mass spectrometry to shows that KRAS phosphorylation via Src alters the conformation of switch I and II regions and thereby impacts the GTPase cycle.
