Proceedings of the National Academy of Sciences · 2008 · 106 citations · 24 references
MedicineCancer BiologyOncologyCell SignalingMolecular OncologySignal TransductionCancer Cell SignalingCyclin-dependent KinasesGlioblastomaGrowth Factor SignalingProtein Kinase CascadesSignal Transduction In CancerGlioblastoma InvasionGlioblastoma Tumor BiologyPhosphatidylinositol 3-Kinase PathwayPhosphatidylinositol 3-Kinase-akt PathwayPhosphatidylinositol 3-Kinase-akt SignalingPhosphoinositide 3-Kinase-akt ActivationPi3 Kinase-akt SignalingPi3k-akt Signaling Pathway
Isoform A of phosphatidylinositol 3-kinase enhancer (PIKE-A) is a newly identified prooncogenic factor that has been implicated in cancer cell growth. How PIKE-A activity is regulated in response to growth signal is poorly understood. Here, we demonstrate that cyclin dependent kinase 5 (Cdk5), a protein known to function mainly in postmitotic neurons, directly phosphorylates PIKE-A at Ser-279 in its GTPase domain in glioblastoma cells. This phosphorylation event stimulates PIKE-A GTPase activity and the activity of its downstream effector Akt. Growth signal activates Cdk5 and results in a Cdk5-dependent accumulation of phosphorylated PIKE-A and activation of Akt in the nucleus. Furthermore, PIKE-A phosphorylation and Cdk5 are increased in human glioblastoma specimens. Phosphorylation of PIKE-A by Cdk5 mediates growth factor-induced migration and invasion of human glioblastoma cells. Together, these findings identify PIKE as the first Cdk5 target in cancer cells, revealing a previously undescribed regulatory mechanism that mediates growth signal-induced activation of PIKE-A/Akt and tumor invasion.
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Melissa M. Fraser, Xiaoyan Zhu, Chang-Hyuk Kwon et al. · Cancer Research · 2004 · 217 citations · Full text
Medicine, Neuroscience, Oncology +17
Patrice D. Smith, Matthew Mount, Raj Shree et al. · Journal of Neuroscience · 2006 · 180 citations · Full text