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Phosphatidylinositol trisphosphate binds PDPK1. 57 / 63
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"PIP3 binds to pyruvate dehydrogenase kinase 1 (PDK1) and Akt, and co-localizes them at the plasma membrane."
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"PDK1 exhibits constitutive kinase activity (Fruman et al., 2017), and the PIP3-dependent recruitment of PDK1 and Akt brings them to vicinity resulting in PDK1-induced Akt phosphorylation (Figure 5C)."
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"PDK1 with its PH domain binds to either PIP3 or PIP2 and is translocated to the plasma membrane."
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"PH domain-containing proteins AKT and PDK1 bind to PIP3, then PDK1 phosphorylates AKT at T308 to activate AKT."
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"Akt and PDK1 bind PIP3 and translocate to the membrane [XREF_BIBR, XREF_BIBR]."
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"The PI3K family consists of three classes, Class I, Class II and Class III, among which the Class I PI3Ks are responsible for the production of PIP3, which binds to the pleckstrin homology domain of AKT and phosphoinoside dependent protein kinase 1 (PDK1), resulting in the phosphorylation of AKT [XREF_BIBR - XREF_BIBR]."
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"Subsequently, PIP3 binds to Akt and PDK1, and PDK1 phosphorylates the Akt protein, activating downstream signaling pathways such as the mTOR and Bax signaling pathways (66,67), consequently influencing various biological behaviors of cells."
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"PDK1 and PKB and Akt bind to PIP3 and are recruited to the membrane XREF_BIBR, XREF_BIBR resulting in the phosphorylation of Akt by PDK1 and activation of Akt which leads to phosphorylation of both S6K and 4EBP1 XREF_BIBR, XREF_BIBR, XREF_BIBR, XREF_BIBR, XREF_BIBR - XREF_BIBR, XREF_BIBR, XREF_BIBR, XREF_BIBR."
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"This prevents PDK1 binding to PIP3 and leads to failure to activate PKB and to phosphorylate PKB downstream targets including, TSC2, GSK-3α/β, FOXO-1 and -3, WNK1 and PRAS-40."
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"PIP3, a product of PI3K, binds to AKT and leads to the membrane recruitment of AKT and also binds to phosphoinositide dependent kinase 1 (PDK1) via their pleckstrin homology (PH) domains, and then PDK1 phosphorylates AKT in the kinase domain (Thr 308 in AKT1)."
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"Because PDK1 binding to PIP3 is required for Akt activation [43], these data suggest that Akt is not involved in PDK1 mediated tumorigenesis."
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"PIP3 binds to AKT and PDK1, causing PDK1 to phosphorylate Ser308 and Ser473 of the AKT protein, resulting in activation of AKT."
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"When PI3K is activated, it can induce the conversion of phosphatidylinositol 3,4-bisphosphate (PIP2) to 3,4,5-trisphosphate (PIP3), and then PIP3 can bind to PDK1 and phosphorylate AKT [45]."
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"Furthermore, the binding of PDK1 to PIP3 facilitates the rate at which PDK1 phosphorylates and activates PKB ."
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"PIP3 binds and localizes the 3-phosphoinositide-dependent protein kinase-1 (PDK1) to the cell membrane, along with PDK1 's targets, Akt and atypical protein kinase C (aPKC)."
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"Deacetylation by SIRT1 enhanced binding of Akt and PDK1 to PIP3 to promote their membrane localization, resulting in their activation [ 52 ]."
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"PIP3 is bound by AKT which facilities its activation by PDK1."
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"PIP3 then binds to 3-phosphoinositide-dependent protein kinase 1 (PDK1) and activates it."
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"PIP3 then binds to 3-phosphoinositide-dependent protein kinase 1 (PDK1) and activates it."
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"PIP3, a product of PI3K, binds to AKT and leads to the membrane recruitment of the AKT, and it also binds to phosphoinositide dependent kinase 1 (PDK1) via their pleckstrin homology (PH) domains, then PDK1 phosphorylates AKT in the kinase domain (Thr 308 in AKT1)."
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"Beside the PDK1 kinase activity, beta3 integrin endocytosis and FA dynamics require also the PDK1 binding to PIP3, downstream to PI3K activation."
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"PIP3 binds AKT and PDK1 and promotes the phosphorylation of AKT at Thr308."
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"Indeed, PIP3 binds AKT and PDK1, and as a result, they can accumulate near the membrane [107]."
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"PDK1 strongly binds with PIP3, the lipid product of PI3K and gets activated that result in translocation to the cell membrane."
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"PIP3 recruits Akt to the plasma membrane and binds to pyruvate dehydrogenase kinase 1 (PDK1), which phosphorylates Akt."
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"PIP3 binds to 2 other kinases, Akt and PDK1."
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"PIP3 binds to the PH-domain signaling proteins AKT and PDK1 to promote the phosphorylation of AKT and thus activate AKT [119] ."
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"The PIP3, a product of PI3K, binds to AKT and leads to the membrane recruitment of the AKT, and it also binds to phosphoinositide dependent kinase 1 (PDK1) via their pleckstrin homology (PH) domains, then PDK1 phosphorylates AKT in the kinase domain (Thr 308 in AKT1)."
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"Under high amino acid availability, a Class III PI3K (Vsp34) is activated and through the recruitment of PIP3 and PDK, activates Akt, which then has two means of activating mTOR."
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"PIP3 binds and activates PDK1 and PDK2 (3-phosphoinositide dependent protein kinases 1 and 2)."
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"PIP3 binds to Akt and PDK1 (phosphoroside dependent kinase-1), which contains PH domain in the cell, and promotes the phosphorylation of ser308 of Akt by PDK1, leading to Akt activation."
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"PIP3 also binds to 3-phosphoinositide-dependent protein kinase 1 (PDPK1, also known as Protein Kinase B)."
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"AKT and PDK1 bind to PIP3 at the plasma membrane, and PDK1 phosphorylates the activation loop of AKT at Thr 308 to expose Ser 473 that is phosphorylated by several kinases (PDK2 and others) to achieve[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
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"Next, PIP3 binds to PDK1 and AKT proteins, leading to phosphorylation of AKT protein by PDK1 and activation of numerous enzymes."
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"PIP3 binds to intracellular the signaling proteins AKT and PDK1, and phosphorylates AKT through PDK1 to enhance its activity."
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"PIP3 binds to the intracellular signaling protein PDK1, thereby activating AKT."
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"Phosphoinositide-dependent kinase 1 (PDK1) also binds to PIP3 and phosphorylates threonine 308, a kinase domain of Akt, which contributes to the stabilization of the activation loop [74,75,76]."
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"Ceramide secondly prevent the translocation of AKT to the PIP3-PDK1 complex in the plasma membrane."
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"PDK1 interacts with PKCzeta and phosphorylates the kinase domain at threonine 410 and then interacts with PIP3 to create stable activation."
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"PDK1 binds PIP3 at the plasma membrane and subsequently activates AKT, which negatively regulates tuberous sclerosis protein complex 1 (TSC1) and TSC2, resulting in the activation of mTOR in a complex[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
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"A good example of feed-forward regulation is the activation of the protein kinase Akt by the lipid second messanger PIP3 (PIP3 binds Akt, which promotes Akt activation, and PIP3 also stimulates the kinase PDK1, which phosphorylates Akt and further contributes to Akt activation)."
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"This modification hampered the binding of PDK1 to PIP3, whereas deacetylated form of PDK1 displayed opposite results, thus suggesting that acetylation dependent regulation could be a common mechanism controlling activity of the membrane-lipid binding proteins."
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"To further examine the regulation of Akt1 activation, we studied PDK1, an upstream regulatory kinase, whose PH domain binds to the PI 3-K product PIP3 with high affinity."
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"Phosphoinositide-dependent kinase 1 (PDK1) binds PIP3 in the plasma membrane where it activates AKT, which itself binds PIP3, by phosphorylating AKT-Thr308."
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"While AKT and PDK1 bind to PIP3 at the plasma membrane, PDK1 phosphorylates the activation loop of AKT at T308."
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"Accumulating PIP3 binds to PDK1, in turn activating the AKT-mTorc1 pathway 38."
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"In the membrane, the PDK1 and PIP3 complex phosphorylates AKT on thr308 XREF_BIBR."
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"Akt and PDK1 bind to PIP3 at the plasma membrane, and PDK1 phosphorylates the activation loop of Akt at T308."
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"Accordingly, PIP3 can interact with PDK1 to directly activate a variety of PKC isoforms."
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"PI3K-generated PIP3 can bind to PDK1 (3-Phosphoinositide-dependent kinase 1) to induce PDK1 activation."
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"PIP3 binds and recruits the kinases PDK1 and Akt, leading to Akt phosphorylation on T308 and S473 by PDK1 and mTORC2, respectively; both of these phosphorylation events are required for full Akt activation."
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"This process induces the membrane translocation of 3-phosphoinositide-dependent protein kinase-1 (PDK1) that binds to PIP3 with its PH (Pleckstrin Homology) domain triggering a cascade of second messe[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
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"Subsequently, PIP3 binds to specific structural domains, facilitating the recruitment of AKT to its kinase PDK1, thereby activating PKB/AKT (27)."
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"Once activated, PI3K can phosphorylate the phosphatidylinositol 4,5-bisphosphate (PIP2) that transforms to PtdIns(3,4,5) P3 (PIP3), which recruits AKT to the membrane, where it is phosphorylated by th[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
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"PIP3 then binds to Phosphatidylinositol-dependent Protein Kinase 1 (PDK1), which facilitates the phosphorylation of Akt at the Thr308 site."
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"Second, ceramide blocks insulin stimulated Akt translocation to the PIP3 and PDK1 complex at the plasma membrane [XREF_BIBR, XREF_BIBR]."
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"PDK1 binds to PIP3 at the plasma membrane, which can phosphorylate AKT at Thr , suggesting STEAP4 overexpression reduced the interaction of AKT and PDK1, reducing the phosphorylation of AKT.To determine whether STEAP4 inhibited chemotherapy resistance through inhibiting PI3K/AKT pathway, we knocked down AKT in STEAP4 knockdown cells (Fig. 6a), colony formation assay showed that inhibition of AKT and STEAP4 significantly increased DDP-induced proliferation arrest (Fig. 6b), and apoptosis assay showed that inhibition of AKT and STEAP4 also increased DDP-induced apoptosis (Fig. 6c)."
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