![pip3 pathway pip3 pathway](https://blog.infino.me/wp-content/uploads/2019/09/IP4-and-IP7-negatively-regulate-Akt-signaling-IP4-and-IP7-are-cytosolic-PIP3-analogs.png)
It is made by hydrolysis of phosphatidylinositol 4,5-bisphosphate (PIP 2), a phospholipid that is located in the plasma membrane, by phospholipase C (PLC). Many genes belonging to the PI3K/Akt pathway have been implicated in the pathophysiology of solid tumors and sensitivity/resistance to chemotherapy. Inositol trisphosphate or inositol 1,4,5-trisphosphate abbreviated InsP 3 or Ins3P or IP 3 is an inositol phosphate signaling molecule. Once localized at the cell plasma membrane, Akt is phosphorylated and stimulates protein synthesis and cell growth by activating mammalian target of rapamycin (mTOR) through effects on the. Activated Akt is involved in the downstream mTORC1 mediated response to biogenesis of protein and ribosome. PIP3 acts as a docking site for Akt, a serine/threonine kinase that is the central mediator of the PI3K pathway, and phosphoinositide-dependent kinase 1. PIP3 will recruit the downstream Akt to inner membranes and phosphorylates Akt on its serine/threonine kinase sites (Thr308 and Ser473). Activated p110 phosphorylated the PIP2 into the second messenger PIP3, and this reaction can be reversed by the PI3K antagonist PTEN. Upon ligand binding, phosphorylated tyrosine residing in activated RTKs will bind to p85, then release the catalytic subunit p110. The mTORC1 complex is made up of mTOR, Raptor, mLST8, and PRAS40, and the mTORC2 complex is composed of mTOR, Rictor, Sin1, and mLST8.
![pip3 pathway pip3 pathway](https://www.frontiersin.org/files/Articles/31787/fonc-02-00109-HTML/image_m/fonc-02-00109-g001.jpg)
mTOR is a key protein evolutionarily conserved from yeast to man and is essential for life. Akt kinases belong to the AGC kinase family, related to AMP/GMP kinases and protein kinase C. Class I PI3Ks are heterodimers composed of a catalytic (CAT) subunit (i.e., p110) and an adaptor/regulatory subunit (i.e., p85), and can be further divided into two subclasses: subclass IA (PI3Kα, β, and δ), which is activated by receptors with protein tyrosine kinase activity, and subclass IB (PI3Kγ), which is activated by receptors coupled with G proteins. The PI3K/Akt/mTOR signaling pathways is crucial to many aspects of cell growth and survival, in physiological as well as in pathological conditions.