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PI3 K/Akt/mTOR SIGNALING
The PI3K/AKT/mTOR pathway is an intracellular signaling pathway important in apoptosis and hence cancer e.g. breast cancer and glioblastoma. The phosphatidylinositol 3-kinases (PI3Ks) are a family of lipid kinases whose primary biochemical function is to phosphorylate the 3-hydroxyl group of phosphoinositides PI3K activation activates AKT. AMP-activated protein kinase (AMPK) was initially identified as a serine/threonine kinase that negatively regulates several key enzymes of the lipid anabolism. AMPK is regarded as the major energy-sensing kinase that activates a whole variety of catabolic processes in multicellular organisms such as glucose uptake and metabolism, while simultaneously inhibiting several anabolic pathways, such as lipid, protein, carbohydrate biosynthesis and mTOR.
The proline-rich Akt substrate of 40 kDa (PRAS40) acts at the intersection of the Akt- and mammalian target of rapamycin (mTOR)-mediated signaling pathways. The protein kinase mTOR is the catalytic subunit of two distinct signaling complexes, mTOR complex 1 (mTORC1) and mTORC2, that link energy and nutrients to the regulation of cellular growth and energy metabolism. Alterations in Akt and mTOR activity have been linked to the progression of multiple diseases such as cancer and type 2 diabetes.
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FREE REVIEW ARTICLES.
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mTOR signaling in glioblastoma: lessons learned from bench to bedside. , David Akhavan, Timothy F. Cloughesy, and Paul S. Mischel Neuro Oncology, Aug 2010; 12: 882 – 889.
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mTOR and the differentiation of mesenchymal stem cells. , Xinxin Xiang, Jing Zhao, Geyang Xu, Yin Li, and Weizhen Zhang. Acta Biochim Biophys Sin, Jul 2011; 43: 501 - 510
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mTor Signaling in Skeletal Muscle During Sepsis and Inflammation: Where Does It All Go Wrong? Robert A. Frost and Charles H. Lang. Physiology, Apr 2011; 26: 83 - 96.
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Role of AMPK-mTOR-Ulk1/2 in the Regulation of Autophagy: Cross Talk, Shortcuts, and Feedbacks., Sebastian Alers, Antje S. Löffler, Sebastian Wesselborg, and Björn Stork. Mol. Cell. Biol., Jan 2012; 32: 2 - 11.
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Status of PI3K inhibition and biomarker development in cancer therapeutics., B. Markman, F. Atzori, J. Pérez-García, J. Tabernero, and J. Baselga. Ann. Onc., Apr 2010; 21: 683 - 691
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Pushing the Envelope in the mTOR Pathway: The Second Generation of Inhibitors., Eduardo Vilar, Jose Perez-Garcia, and Josep Tabernero. Mol. Cancer Ther., Mar 2011; 10: 395 - 403.
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PI3K
in hypertension: a novel therapeutic target controlling vascular myogenic tone and target organ damage., Daniela Carnevale and Giuseppe Lembo. Cardiovasc Res, Sep 2012; 95: 403 - 408.
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