Endokrinologie und metabolisches Syndrom
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Metabolical Activities of Phosphoinositide 3-Kinase Pathway and its Connection to Non-Classical Actions of Thyroid Hormones

Souza GS, Moraes BC, Carvalho TM and Conde SJ

Mutations in biochemical pathways mediators are often found in cancer, and it is observed that via phosphoinositide 3-kinase (PI3K) is associated with tumor development and progression. This pathway is involved in several metabolic processes, including regulation of gene expression by non-classical actions of thyroid hormone. The objective of this paper is to provide a brief literature review of progress in information obtained on the PI3K on the last fifteen years. It was used the PubMed database, with the assistance of MeSh (Medical Subject Headings) and as descriptor "Phosphoinositide 3-Kinase" AND "Thyroid Hormones" to the selection of base articles, and later were included references found in those to complement the review. It stands between the information obtained from them that PI3Ks are lipid kinases that phosphorylate the 3-OH group of moderatory inositol molecules of cellular functions regulatory proteins. The PI3K pathway is involved in a wide variety of cellular processes, including intracellular traffic, cytoskeletal organization, apoptosis prevention, cell growth and transformation and it is important for various cell lineages differentiation. This pathway inhibitors promoted multiple possibilities of experiments, which led to the discovery of a relationship between PI3K pathway and other proteins such as protein kinase B (also known as AKT), mammalian target of rapamycin (mTOR) and oncoprotein RAS. The via was also associated with the expression of cancer related genes and hormones, including thyroid hormone. Thyroid hormones (TH) can work by other mechanisms besides the classical pathway, which occurs through receptors and responsive elements. The alternative to it is the non-classical or non-genomic pathway, in which TH activates PI3K, either by binding to TRβ or to αvβ3 integrin. This activation results in the transcription of specific genes, such as hypoxia inducing factor (HIF-1α) glucose transporter 1 (GLUT1), calcineurin inhibitor (ZAKI4α), among others.