loading...| Preferred Name | PIP3 activates AKT signaling | |
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| Definitions |
Reviewed: Yuzugullu, Haluk, 2012-08-13 Signaling by AKT is one of the key outcomes of receptor tyrosine kinase (RTK) activation. AKT is activated by the cellular second messenger PIP3, a phospholipid that is generated by PI3K. In ustimulated cells, PI3K class IA enzymes reside in the cytosol as inactive heterodimers composed of p85 regulatory subunit and p110 catalytic subunit. In this complex, p85 stabilizes p110 while inhibiting its catalytic activity. Upon binding of extracellular ligands to RTKs, receptors dimerize and undergo autophosphorylation. The regulatory subunit of PI3K, p85, is recruited to phosphorylated cytosolic RTK domains either directly or indirectly, through adaptor proteins, leading to a conformational change in the PI3K IA heterodimer that relieves inhibition of the p110 catalytic subunit. Activated PI3K IA phosphorylates PIP2, converting it to PIP3; this reaction is negatively regulated by PTEN phosphatase. PIP3 recruits AKT to the plasma membrane, allowing TORC2 to phosphorylate a conserved serine residue of AKT. Phosphorylation of this serine induces a conformation change in AKT, exposing a conserved threonine residue that is then phosphorylated by PDPK1 (PDK1). Phosphorylation of both the threonine and the serine residue is required to fully activate AKT. The active AKT then dissociates from PIP3 and phosphorylates a number of cytosolic and nuclear proteins that play important roles in cell survival and metabolism. For a recent review of AKT signaling, please refer to Manning and Cantley, 2007. Reviewed: Greene, LA, 2007-11-08 15:39:37 Reviewed: Zhao, Jean J, 2012-08-13 Reviewed: Thorpe, Lauren, 2012-08-13 |
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http://purl.obolibrary.org/obo/HINO_0016078 |
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Reviewed: Yuzugullu, Haluk, 2012-08-13 Signaling by AKT is one of the key outcomes of receptor tyrosine kinase (RTK) activation. AKT is activated by the cellular second messenger PIP3, a phospholipid that is generated by PI3K. In ustimulated cells, PI3K class IA enzymes reside in the cytosol as inactive heterodimers composed of p85 regulatory subunit and p110 catalytic subunit. In this complex, p85 stabilizes p110 while inhibiting its catalytic activity. Upon binding of extracellular ligands to RTKs, receptors dimerize and undergo autophosphorylation. The regulatory subunit of PI3K, p85, is recruited to phosphorylated cytosolic RTK domains either directly or indirectly, through adaptor proteins, leading to a conformational change in the PI3K IA heterodimer that relieves inhibition of the p110 catalytic subunit. Activated PI3K IA phosphorylates PIP2, converting it to PIP3; this reaction is negatively regulated by PTEN phosphatase. PIP3 recruits AKT to the plasma membrane, allowing TORC2 to phosphorylate a conserved serine residue of AKT. Phosphorylation of this serine induces a conformation change in AKT, exposing a conserved threonine residue that is then phosphorylated by PDPK1 (PDK1). Phosphorylation of both the threonine and the serine residue is required to fully activate AKT. The active AKT then dissociates from PIP3 and phosphorylates a number of cytosolic and nuclear proteins that play important roles in cell survival and metabolism. For a recent review of AKT signaling, please refer to Manning and Cantley, 2007. Reviewed: Greene, LA, 2007-11-08 15:39:37 Reviewed: Zhao, Jean J, 2012-08-13 Reviewed: Thorpe, Lauren, 2012-08-13 |
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| definition source |
Pubmed17604717 Reactome, http://www.reactome.org |
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PIP3 activates AKT signaling |
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| prefixIRI |
HINO:0016078 |
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| prefLabel |
PIP3 activates AKT signaling |
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| seeAlso |
Reactome Database ID Release 431257604 ReactomeREACT_75829 |
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http://purl.obolibrary.org/obo/HINO_0009542 http://purl.obolibrary.org/obo/HINO_0016084 http://purl.obolibrary.org/obo/HINO_0016083 http://purl.obolibrary.org/obo/HINO_0009490 http://purl.obolibrary.org/obo/HINO_0009488 http://purl.obolibrary.org/obo/HINO_0009518 http://purl.obolibrary.org/obo/HINO_0009517 http://purl.obolibrary.org/obo/HINO_0009519 http://purl.obolibrary.org/obo/HINO_0016077 http://purl.obolibrary.org/obo/HINO_0009534 http://purl.obolibrary.org/obo/HINO_0009533 |