The phoshatidylinositol-3 kinase (PI3K) can be activated by binding directly or via the protein IRS-1 to the activated receptor tyrosine kinase. Alternatively, PI3K can be activated by binding to the GTP-bound form of the membrane bound protein Ras. Active PI3K catalyzes the formation of...
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The second messenger PIP3 formed by PI3K can be hydrolyzed to PIP2 by the phosphatase PTEN. PIP2 can be hydrolyzed to diacyl glycerol (DAG) and inositol trisphosphate (IP3) by phospholipase C (PLC). IP3 dissociates from the membrane into the cell, where it opens channels of intracellular...
The phosphatase PTEN dephosphorylates PIP3 to PIP2, which can then be hydrolyzed to DAG and IP3. In addition, PTEN performs many other functions by binding to and activating or inactivating several nuclear proteins. Through these effects PTEN activates DNA repair and inhibits...
In tumor cells of patients with congenital hamartoma syndromes such as Cowden syndrome (CS), tuberous sclerosis complex (TSC) syndrome and Peutz-Jeghers syndrome, the phosphatidylinositol 3-kinase (PI3K) and the mammalian target of rapamycin complex 1 (mTORC1) are overactivated. Major...
In normal cells without a Wnt signal a cytosolic destruction complex phosphorylates the signaling protein b-catenin leading to its degradation. In the presence of the extracellular Wnt factor, activation of the membrane bound receptor FZD leads to the dissociation of the destruction...
