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Understanding the Warburg Effect: The Metabolic Requirements of Cell Proliferation
It is proposed that the metabolism of cancer cells, and indeed all proliferating cells, is adapted to facilitate the uptake and incorporation of nutrients into the biomass needed to produce a new cell.
The phosphoinositide 3-kinase pathway.
- L. Cantley
- Biology, ChemistryScience
- 31 May 2002
The PI3K pathway is implicated in human diseases including diabetes and cancer, and understanding the intricacies of this pathway may provide new avenues for therapuetic intervention.
AKT/PKB Signaling: Navigating Downstream
MET Amplification Leads to Gefitinib Resistance in Lung Cancer by Activating ERBB3 Signaling
It is proposed that MET amplification may promote drug resistance in other ERBB-driven cancers as well after it was found that amplification of MET causes gefitinib resistance by driving ERBB3 (HER3)–dependent activation of PI3K, a pathway thought to be specific to EGFR/ERBB family receptors.
Cancer-associated IDH1 mutations produce 2-hydroxyglutarate
It is shown that cancer-associated IDH1 mutations result in a new ability of the enzyme to catalyse the NADPH-dependent reduction of α-ketoglutarate to R(-)-2-hydroxyglutarate (2HG), and that the excess 2HG which accumulates in vivo contributes to the formation and malignant progression of gliomas.
Scansite 2.0: proteome-wide prediction of cell signaling interactions using short sequence motifs
Scansite identifies short protein sequence motifs that are recognized by modular signaling domains, phosphorylated by protein Ser/Thr- or Tyr-kinases or mediate specific interactions with protein or phospholipid ligands, allowing segments of biological pathways to be constructed in silico.
The evolution of phosphatidylinositol 3-kinases as regulators of growth and metabolism
In light of the recent advances in understanding of the function of PI3Ks in the pathogenesis of diabetes and cancer, the exciting therapeutic opportunities for targeting this pathway to treat these diseases are discussed.
The tumor suppressor LKB1 kinase directly activates AMP-activated kinase and regulates apoptosis in response to energy stress.
- R. Shaw, Monica Kosmatka, L. Cantley
- BiologyProceedings of the National Academy of Sciences…
- 9 March 2004
AMP-activated protein kinase (AMPK) is a highly conserved sensor of cellular energy status found in all eukaryotic cells. AMPK is activated by stimuli that increase the cellular AMP/ATP ratio.…
The Kinase LKB1 Mediates Glucose Homeostasis in Liver and Therapeutic Effects of Metformin
It is shown that metformin, one of the most widely prescribed type 2 diabetes therapeutics, requires LKB1 in the liver to lower blood glucose levels, and TORC2 is a critical target of L KB1/AMPK signals in the regulation of gluconeogenesis.
The pathways of phosphoinositide synthesis and the enzymes involved are re-examine and previous hypotheses about the substrate selectivity of different phosphoinposide kinase families are challenged.