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Pip3 pathway1/9/2024 ![]() ^ Traynor-Kaplan AE, Harris AL, Thompson BL, Taylor P, Sklar LA (July 1988)."Type I phosphatidylinositol kinase makes a novel inositol phospholipid, phosphatidylinositol-3-phosphate". ^ Whitman M, Downes CP, Keeler M, Keller T, Cantley L (April 1988).In the absence of such an interaction, memory consolidation is impaired. Of these proteins, Phldb2 has been shown to interact with PIP3 to induce and maintain long-term potentiation. PIP3 interacts with proteins to mediate synaptic plasticity. Moreover, PIP3 suppression disrupts normal AMPA expression on the neuron membrane and instead leads to the accumulation of AMPA on dendritic spines, commonly associated with synaptic depression. Here, PIP3 has been implicated in regulating synaptic strengthening and AMPA expression, contributing to long-term potentiation. PIP3 plays a critical role outside the cytosol, notably at the postsynaptic terminal of hippocampal cells. Such proteins include Akt/PKB, PDPK1, Btk1, and ARNO. The PH domain in a number of proteins binds to PtdIns(3,4,5) P 3. PtdIns(3,4,5) P 3 is dephosphorylated by the phosphatase PTEN on the 3 position, generating PI(4,5)P 2, and by SHIPs ( SH2-containing inositol phosphatase) on the 5' position of the inositol ring, producing PI(3,4)P 2. PIP 3 functions to activate downstream signaling components, the most notable one being the protein kinase Akt, which activates downstream anabolic signaling pathways required for cell growth and survival. Subsequent studies demonstrated that in vivo the enzyme originally identified by Cantley's group prefers PtdIns(4,5)P2 as a substrate, producing the product PIP3. Working independently, Alexis Traynor-Kaplan and coworkers published a paper demonstrating that a novel lipid, phosphatidylinositol 3,4,5 trisphosphate (PIP3) occurs naturally in human neutrophils with levels that increased rapidly following physiologic stimulation with chemotactic peptide. Cantley published a paper describing the discovery of a novel type of phosphoinositide kinase with the unprecedented ability to phosphorylate the 3' position of the inositol ring resulting in the formation of phosphatidylinositol-3-phosphate (PI3P).
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