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PDBsum entry 3x0c
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References listed in PDB file
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Key reference
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Title
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The lipid kinase pi5p4kβ is an intracellular gtp sensor for metabolism and tumorigenesis.
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Authors
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K.Sumita,
Y.H.Lo,
K.Takeuchi,
M.Senda,
S.Kofuji,
Y.Ikeda,
J.Terakawa,
M.Sasaki,
H.Yoshino,
N.Majd,
Y.Zheng,
E.R.Kahoud,
T.Yokota,
B.M.Emerling,
J.M.Asara,
T.Ishida,
J.W.Locasale,
T.Daikoku,
D.Anastasiou,
T.Senda,
A.T.Sasaki.
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Ref.
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Mol Cell, 2016,
61,
187-198.
[DOI no: ]
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PubMed id
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Abstract
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While cellular GTP concentration dramatically changes in response to an
organism's cellular status, whether it serves as a metabolic cue for biological
signaling remains elusive due to the lack of molecular identification of GTP
sensors. Here we report that PI5P4Kβ, a phosphoinositide kinase that regulates
PI(5)P levels, detects GTP concentration and converts them into lipid second
messenger signaling. Biochemical analyses show that PI5P4Kβ preferentially
utilizes GTP, rather than ATP, for PI(5)P phosphorylation, and its activity
reflects changes in direct proportion to the physiological GTP concentration.
Structural and biological analyses reveal that the GTP-sensing activity of
PI5P4Kβ is critical for metabolic adaptation and tumorigenesis. These results
demonstrate that PI5P4Kβ is the missing GTP sensor and that GTP concentration
functions as a metabolic cue via PI5P4Kβ. The critical role of the GTP-sensing
activity of PI5P4Kβ in cancer signifies this lipid kinase as a cancer
therapeutic target.
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