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PDPK1 phosphorylates AKT1. 111 / 116
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"PI3K-independent AKT1 phosphorylation and activation by PDK1."
20361045
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"The binding of circAmotl1 to 3-phosphoinositide-dependent protein kinase 1 (PDK1) and protein kinase B (AKT1) facilitates the PDK1-dependent phosphorylation of AKT1 [ xref ]."
32751850
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"For instance, circ-AMOTL1 functions as a scaffold that facilitates the phosphorylation of AKT1 by PDK1 [ xref ]."
34205978
rlimsp
"It involves TRAF6, Skp2 (SKP1 interacting partner 2) and NEDD4-1 enhanced nuclear translocation of Akt1 after its prior phosphorylation (pT308/pS473) by PDK1 and mTORC2 [73]."
29562639
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"PI3k activates phosphatidylinositol 3, 4, 5-triphosphate (PIP3), which triggers phosphoinositide-dependent protein kinase (PDK), promoting protein kinase B (Akt) phosphorylation in threonine 308 and serine 473 residues."
37630775
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"Upon PI3K activation and/or PTEN inactivation, PDPK1 is recruited to the plasma membrane and phosphorylates AKT1 at threonine 308 (AKT1-T308), thus leading to its activation [XREF_BIBR]."
33544134
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"In addition, AKT1 can be phosphorylated by PDK1, and it is also the kinase of YAP."
38506089
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"Akt1 is phosphorylated by PDK1, and thereby activated upon translocation to the membrane [22,23] ."
12928036
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"PDK1 phosphorylates members of the protein kinase C (PKC) family, serum/glucocorticoid regulated kinase (SGK), protein kinase B (PKB/Akt), p70 ribosomal protein S6 kinase (p70S6K), and p90 ribosomal protein S6 kinase (p90RSK) [8,9]."
35681431
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"Subsequent studies showed the compounds bind to the PH domain maintaining the kinase in a closed formation preventing PDK1 phosphorylation of Akt1 and reducing Akt1 phosphorylation of the downstream s[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
21256157
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"Phosphorylation of PI(4,5)P 2 to PI(3,4,5)P 3 by PI3K activates the PH-domain-containing kinase 3-phosphoinositide dependent protein kinase 1 (PDPK1), which in turn phosphorylates serine/threonine kinase AKT serine/threonine kinase 1 (AKT) [ xref ]."
33775061
rlimsp
"Activated α2-Macroglobulin Binding to Cell Surface GRP78 Induces T-Loop Phosphorylation of Akt1 by PDK1 in Association with Raptor."
24516643
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"Meanwhile, phosphorylation of C-terminal S477/T479 residues by CDK2/cyclin A2 or mTORC2, together with phosphorylation of S473, synergistically promotes the phosphorylation of Akt1 by PDK1 [81, 89]."
34419139
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"PIP3 generates membrane-docking sites for both Phosphotidylinositol-Dependent Kinase 1 (PDK1) and for the serine/threonine protein kinase AKT-1 through their pleckstrin homology domains, where PDK1 phosphorylates and activates AKT-1 ( xref – xref )."
25009292
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"Akt1 is phosphorylated by PDK1, and thereby activated upon translocation to the membrane ( Fig. 2 A )."
17118696
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"In addition, AKT1 can be phosphorylated by PDK1, and it is also the kinase of YAP."
38506089
rlimsp
"In contrast, the PIF-binding pocket of PDK1 is not required for the phosphorylation of PKBalpha by PDK1."
11500365
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"Therefore, after phosphorylation of Akt1 by the PDK1 at the membrane, a conformational change occurs ( xref ), and Akt1 detaches from the membrane, leaving less Akt1 on the membrane at the time of observation."
18823366
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"PDK1 phosphorylates Akt1 at T308 in its activation loop ( xref ), while mTORC2 is widely believed to phosphorylate S473 in its hydrophobic motif ( xref )."
40168118
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"5 Phosphoinositide 3,4,5-triphosphate (PIP3), the product of PI3K phosphorylation, recruits protein kinase B (PKB) which in turn is phosphorylated by 3-phosphoinositide dependent protein kinase 1 (PDK[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
17869522
rlimsp
"In summary, we have employed PCA as a novel tool to characterize AKT1 phosphorylation by PDK1 and provided direct evidence showing stabilized AKT1 association with PDK1 by the reconstituted IFP is sufficient for AKT1 phosphorylation by PDK1 independent of PI3K and membrane localization."
20361045
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"PtdIns(3,4,5)P 3 and PtdIns(3,4)P 2 are recognized as second messengers that govern many downstream events by activating target protein kinases such as PDK1, which subsequently phosphorylate various s[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
19942142
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"PDPK1 phosphorylates and activates AKT1 (Alessi et al., 1996; Alessi et al., 1997)."
35822040
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"Mechanistically, PDK1 phosphorylates AKT1 in a critical activation site at T308 (T309 in AKT2) in the activation loop of the kinase domain, while mTORC2 phosphorylates AKT on S473 (S474 in AKT2) in the C-terminal hydrophobic motif [ xref , xref ]."
28237819
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"In contrast, PDK1 phosphorylates Akt1 at Thr308 and Akt2 at Thr309."
24169049
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"PIP3 generates membrane docking sites for both Phosphotidylinositol Dependent Kinase 1 (PDK1) and for the serine/threonine protein kinase AKT-1 through their pleckstrin homology domains, where PDK1 phosphorylates and activates AKT-1."
25009292
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"In the classical model of Akt1 regulation, phospholipid PIP3 recruits Akt1 to the plasma membrane ( xref ) where it is acted upon by two protein kinases, mTORC2 and PDK1, which phosphorylate Akt1 on its C-terminus (Ser473) and activation loop (Thr308), respectively ( xref ; xref ; xref )."
30078705
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"PDK1 and PDK2 phosphorylate AKT (protein kinase B serine/threonine kinase) which in turn inhibits the TSC complex."
27525138
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"PI3K phosphorylates the membrane phospholipid phosphatidylinositol-4,5-bisphosphate to phosphatidylinositol 3,4,5 trisphosphate, recruiting PDK1 (a Ser/Thr kinase), which can phosphorylate and activate protein kinase B (AKT)."
27731505
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"PDK1 phosphorylates Akt1 at Thr xref , suggesting that another protein kinase, namely PDK2, is responsible for Ser 473 phosphorylation."
29200866
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"Hence, when PIP3 levels increase in the cell membrane, both kinases are recruited to the membrane, which increases their local concentration and allows the phosphorylation of AKT1 by PDK1 activating d[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
34852218
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"AKT1 is phosphorylated by the PDK1 and by PDK2 [ xref ]."
30781836
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"In the classical model of Akt1 regulation, phospholipid PIP3 recruits Akt1 to the plasma membrane (James et al., 1996) where it is acted upon by two protein kinases, mTORC2 and PDK1, which phosphoryla[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
30078705
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"At the molecular level, the interaction between PDK1 and AKT1 involves the phosphorylation of AKT1 by PDK1."
34852218
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"To install phosphorylation at Thr308, we co-expressed PDK1 and Akt1 while treating cells with phosphatase inhibitor (Fabbro et al., 1999; Kumar et al., 2001) or used recombinant PDK1 to phosphorylate [MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
30078705
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"PIP3 promotes the membrane localization of PDK1 (NM_008960.2) and Akt1 (NM_011062.4), where PDK1 and PDK2 phosphorylate Akt1, resulting in glucose uptake and metabolism."
22253608
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"Binding of the PH domains of both PDK1 and Akt1 to PIP 3 results in their colocalization at the plasma membrane, where PDK1 can phosphorylate and activate Akt1 ( xref , xref )."
33046444
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"Akt/PKB kinase activity depends on two Ras-mediated effector pathways: PI3K, which promotes the PIP3-dependent recruitment of Akt/PKB to the plasma membrane and regulates PDK1 phosphorylation of the Akt/PKB activation loop, and TORC2, which mediates Akt/PKB phosphorylation on the C-terminal hydrophobic motif (Meili ; Funamoto ; Lee ; Kamimura )."
20375144
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"Once recruited, PDK phosphorylates and activates atypical protein kinase C (PKCf) and protein kinase B (Akt), which inhibits 160-kDa protein (AS160), thereby promoting GLUT4 translocation to the plasma membrane."
30843740
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"Akt1 is phosphorylated by PDK1, and thereby activated upon translocation to the membrane [22,23]."
12928036
rlimsp
"PI3K-independent AKT1 phosphorylation and activation by PDK1."
20361045
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"The production of PIP3 drives the recruitment of PDK1 and Akt1 to membranes via their PH domains where Akt1 can be phosphorylated by PDK1 on its activation loop (Thr308) [ xref , xref ]."
30901610
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"PDK1 phosphorylates and activates protein kinase B (AKT) (131)."
36032081
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"PDK1 then phosphorylates AKT1 at one of its two key sites, T308."
30875364
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"This phosphorylation is quite different from PDK1 phosphorylation of Akt and PKBalpha and p70 S6K1."
10469565
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"Overexpression of HA-myr-Akt, which is attached to cell plasma membrane and constitutively phosphorylated by PDK1, marginally reversed isoangustone A-induced p62 degradation and LC3 lipidation ( Fig. [MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
34004245
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"AKT1 phosphorylation is catalyzed by 3-phosphoinositide-dependent kinase 1 (PDK1) and mTORC2 at Thr-308 and Ser-473, respectively (22)."
39006202
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"In contrast, the PIF-binding pocket of PDK1 is not required for the phosphorylation of PKBalpha by PDK1."
11500365
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"In the trans model, activated PDK1 phosphorylates an AKT1 molecule outside its own heterodimer: either a freely diffusing AKT1 monomer or an AKT1 molecule in a different heterodimer."
34673053
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"These lipids, in turn, activate the cytoplasmic factor PDK1, which ultimately phosphorylates Akt (protein kinase B), a key enzyme in the main NT-mediated signaling pathways ( Bowling et al., 2019 )."
36603664
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"Statins also activate phosphoesterinositol-3-kinase (PI-3K) and promote the activation of phosphoinositol-dependent protein kinase (PDK1), which phosphorylates protein kinase B (PKB), improves the insulin sensitivity of the receptor and reduces IR."
39139641
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"Although both IRS are required for insulin-stimulated PDK1 phosphorylation of AKT1 at Thr308/Thr309 (AKT2), phosphorylation of both Thr308/Thr309 and Ser473 (AKT1)/Ser474 (AKT2) is required for maximal activity of AKT (Figure 1) (13, 76)."
37358513
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"Activation of Akt1 is dependent on recruitment of the protein, through its PH domain [ xref ], to the inner side of the plasma membrane, which causes a conformational change [ xref ], allowing PDK1 to phosphorylate threonine 308 (T308) in Akt1’s catalytic domain and mTORC2 to phosphorylate serine 473 (S473) in Akt1’s regulatory domain [ xref , xref ]."
30355958
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"Mechanistically, PDK1 phosphorylates AKT1 in a critical activation site at T308 (T309 in AKT2) in the activation loop of the kinase domain, while mTORC2 phosphorylates AKT on S473 (S474 in AKT2) in the C-terminal hydrophobic motif [XREF_BIBR, XREF_BIBR]."
28237819
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"The active form of PDK1 then triggers the phosphorylation of protein kinase B (Akt) [28]."
38921683
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"PDK-dependent Akt1 phosphorylation is reversed by protein phosphatase 2A (PP2A) which dephosphorylates pT308 and, to a lesser extent, pS473."
25474128
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"PIP3 subsequently recruits pleckstrin homology domain–harboring proteins including pyruvate dehydrogenase kinase 1 (PDK1), mammalian target of rapamycin complex 2 (mTORC2), and protein kinase B (PKB/AKT) to the plasma membrane (16–18), triggering phosphorylation of AKT by PDK1 and mTORC2 and activation of AKT1 and mTORC1 signaling networks (16, 18)."
36791204
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"The mTOR-rictor complex (mTORC2) phosphorylates AKT1 within the carboxy terminus at S473 and PDK1 phosphorylates AKT1 within its activation loop at T308 [ xref , xref ]."
30065942
rlimsp
"AKT1 is phosphorylated by the PDK1 and by PDK2 [14]."
30781836
reach
"Activated alpha 2 -Macroglobulin Binding to Cell Surface GRP78 Induces T-Loop Phosphorylation of Akt1 by PDK1 in Association with Raptor."
24516643
reach
"After phosphoinositide dependent protein kinase (PDK) phosphorylating Akt-1, glycogen synthase kinase (Gsk) 3beta, a serine/threonine kinase, is inhibited."
28066173
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"At the molecular level, the interaction between PDK1 and AKT1 involves the phosphorylation of AKT1 by PDK1."
34852218
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"This brings both kinases in close vicinity and thereby promotes PDK1-dependent phosphorylation of Akt1 at T308 in the activation loop of the catalytic domain [ xref , xref ]."
29562639
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"PDK1 phosphorylates Akt1 to partially activate it and prime it for further activation."
19940154
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"In the cis model, which is more widely presented in the literature ( 43 , 67 , 68 ), the activated PDK1 in a PKD1-AKT1 heterodimer phosphorylates the AKT1 molecule within the same heterodimer."
34673053
sparser
"In summary, we have employed PCA as a novel tool to characterize AKT1 phosphorylation by PDK1 and provided direct evidence showing stabilized AKT1 association with PDK1 by the reconstituted IFP is sufficient for AKT1 phosphorylation by PDK1 independent of PI3K and membrane localization."
20361045
reach
"In the trans model, activated PDK1 phosphorylates an AKT1 molecule outside its own heterodimer: either a freely diffusing AKT1 monomer or an AKT1 molecule in a different heterodimer."
34673053
reach
"Ensemble activity measurements carried out under conditions that closely match those of the single-molecule experiments reveal that PDK1 activates AKT1 via a cis mechanism by phosphorylating an AKT1 m[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
34673053
rlimsp
"However, this mechanism is a less likely possibility because, in the present study, the dynamics of PDK1-mediated phosphorylation of exogenous human Akt1 were similar to those of TORC2-mediated phosphorylation in starfish oocytes."
27390173
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"After phosphoinositide-dependent protein kinase (PDK) phosphorylating Akt-1, glycogen synthase kinase (Gsk) 3β, a serine/threonine kinase, is inhibited (Grimes and Jope, xref ; Hur and Zhou, xref )."
28066173
sparser
"Hence, when PIP3 levels increase in the cell membrane, both kinases are recruited to the membrane, which increases their local concentration and allows the phosphorylation of AKT1 by PDK1 activating d[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
34852218
sparser
"After PIP3 recruits PDK1 and AKT to the cell membrane, PDK1 phosphorylates AKT1 to further activate downstream substrates (protein kinases, E3 ubiquitin ligases, regulators of small G proteins, metabolic enzymes, and transcription factors) [ xref ]."
37238636
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"In addition, the finding that PDK1 and PDK2 sites of E17K-AKT1 are phosphorylated raises the question of whether PDK1 and TORC2 are constitutively associated with the membrane in cells with mutant akt[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
17692802
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"It is also known in other biological systems, that Akt1 and SGK can be phosphorylated and activated by the 3-phosphoinositide-dependent protein kinase 1 (PDK1)."
28297559
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"Akt1 is phosphorylated by PDK1, and thereby activated upon translocation to the membrane ( Fig. 2 A )."
17118696
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"PIP3 boosts phosphoinositide-dependent protein kinase 1 (PDK) which participates in the phosphorylation of protein kinase B (Akt) and allowing phosphorylation of the Rab GTPase-activating protein AS16[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
34048868
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"(8) Then PDK1 phosphorylates and activates protein kinase B (PKB), also referred to as Akt."
20390053
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"Phosphatidylinositol-3,4,5-triphosphate (product of PIP5KA ) activates 3-phosphoinositide-dependent protein kinase-1 (PDPK1), which phosphorylates and activates AKT1 ( Egawa et al., 2002 ) while phosp[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
17239488
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"Phosphatidylinositol-3,4,5-triphosphate (product of PIP5KA ) activates 3-phosphoinositide-dependent protein kinase-1 (PDPK1), which phosphorylates and activates AKT1 ( Egawa et al., 2002 ) while phosp[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
17239488
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"Akt1, Akt2 and Akt3 were phosphorylated and activated by PDK1 at similar rates and to similar extents."
11410335
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"The phosphorylation of Akt (pAkt) by PDK1 activates the kinase to induce autophagy from decreased receptor signaling."
36278355
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"This basal phosphorylation is consistent with our observations that D1 ' has high basal activity relative to the serum stimulated activity level, and that expression of a kinase-inactive PDK1 can decr[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
10469565
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"Therefore, after phosphorylation of Akt1 by the PDK1 at the membrane, a conformational change occurs, and Akt1 detaches from the membrane, leaving less Akt1 on the membrane at the time of observation."
18823366
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"Similarly, compared with full length protein, PKBalpha lacking its PH domain is phosphorylated at a 20-fold lower rate by full length PDK1 [40]."
9838087
sparser
"Although both IRS are required for insulin-stimulated PDK1 phosphorylation of AKT1 at Thr308/Thr309 (AKT2), phosphorylation of both Thr308/Thr309 and Ser473 (AKT1)/Ser474 (AKT2) is required for maximal activity of AKT ( xref ) ( xref , xref )."
37358513
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"Upon PIF peptide binding to PDK1, a conformational change in the active site could increase the interaction of PDK1 with its substrate and, indeed, protein kinase B phosphorylation by PDK1 was increas[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
19135095
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"PIP , in turn, activates the 3-phosphoinositide-dependent protein kinase 1 (PDK-1), which then phosphorylates and activates protein kinases B (AKT1–2) and serum- and glucocorticoid-regulated kinase 1 (SGK-1)."
36936291
rlimsp
"After phosphorylation by PDK1 and mTORC2, AKT becomes activated as phospho-AKT (p-AKT) to activate downstream targets in the nucleus and cytoplasm [27]."
23667466
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"PIP3 in turn recruits PIP3 dependent kinase (PDK), which phosphorylates and activates the survival kinase, protein kinase B (PKB and Akt) (Alessi et al., 1997; Stokoe et al., 1997)."
15766664
sparser
"PIP3 promotes the membrane localization of PDK1 (NM_008960.2) and Akt1 (NM_011062.4), where PDK1 and PDK2 phosphorylate Akt1, resulting in glucose uptake and metabolism."
22253608
sparser
"Allosteric signals can however be boosted by phosphorylation, as in the case of mammalian target of rapamycin complex 2 (mTORC2) and phosphoinositide-dependent protein kinase 1 (PDK1), which phosphorylate AKT1 on its C terminus (Ser473) and activation loop (Thr308), respectively."
34218161
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"Phosphorylation of PI(4,5)P2 to PI(3,4,5)P3 by PI3K activates the PH-domain-containing kinase 3-phosphoinositide dependent protein kinase 1 (PDPK1), which in turn phosphorylates serine/threonine kinase AKT serine/threonine kinase 1 (AKT) [41]."
33775061
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"Phosphorylation of PI(4,5)P2 to PI(3,4,5)P3 by PI3K activates the PH-domain-containing kinase 3-phosphoinositide dependent protein kinase 1 (PDPK1), which in turn phosphorylates serine/threonine kinase AKT serine/threonine kinase 1 (AKT) [41]."
33775061
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"Interestingly, images of the co-location studies showed Akt1 and Hsp90 to be co-localized near the membrane-substrate interface when HAX-1 was expressed, in the region where it is known that Akt1 is phosphorylated by the PI3K and PDK1 axis."
29311840
sparser
"To assess Akt1 mitochondria-nucleus functional connection and the significance of intramitochondrial Akt1 phosphorylation by PDK1, we obtained Akt1 T308A by directed mutagenesis, which renders a non-phosphorylatable mutant at Thr 308 ."
19844585
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"The binding of circAmotl1 to 3-phosphoinositide-dependent protein kinase 1 (PDK1) and protein kinase B (AKT1) facilitates the PDK1 dependent phosphorylation of AKT1 [51]."
32751850
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"This stimulates the phosphoinositide-dependent kinase 1 (PDK1) which then phosphorylates and activates Akt1."
24732012
sparser
"For example, circAmotl1 physically binds to 3-phosphoinositide-dependent protein kinase 1 (PDK1) and protein kinase B (AKT1) to promote PDK1-dependent AKT1 phosphorylation."
32758239
sparser
"The catalytic product of class I PI 3-kinase, PtdIns(3,4,5)P 3 , recruits the protein kinases PDK1 and AKT1 to the plasma membrane, followed by phosphorylation and activation of AKT1 by PDK1 and TORC1[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
19559660
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"The PDK1 plays a central role in cellular signaling through phosphorylating the downstream protein kinase B (Akt) [ 34 ]."
36603508
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"In turn, PIP3 activates phosphatidylinositol-dependent kinase (PDK1) which then phosphorylates protein kinase B (PKB/Akt), among others (reviewed in [119])."
37958659
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"Following its recruitment to the plasma membrane by PIP3, protein kinase B (Akt) is phosphorylated by 3-phosphoinositide-dependent protein kinase 1 (PDK1) [XREF_BIBR, XREF_BIBR]."
28804724
rlimsp
"Activated α2-macroglobulin binding to cell surface GRP78 induces T-loop phosphorylation of Akt1 by PDK1 in association with Raptor."
24516643
reach
"Following its recruitment to the plasma membrane by PIP3, protein kinase B (Akt) is phosphorylated by 3-phosphoinositide-dependent protein kinase 1 (PDK1) [XREF_BIBR, XREF_BIBR]."
28804724
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"In animals, PDK1 can phosphorylate AGC kinases AKT (a.k.a. Protein Kinase B) and S6K, to regulate protein biosynthesis through modulating 40S ribosomal proteins 6S-A (RPS6A) and B (RPS6B), two subunits of ribosomes (Rintelen et al., 2001; Pearce et al., 2010)."
33930167
reach
"Subsequent studies showed the compounds bind to the PH domain maintaining the kinase in a closed formation preventing PDK1 phosphorylation of Akt1 and reducing Akt1 phosphorylation of the downstream s[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
21256157
sparser
"PDPK1 phosphorylates and activates AKT1 ( xref ; xref )."
35822040
sparser
"In the cis model, which is more widely presented in the literature ( 43 , 67 , 68 ), the activated PDK1 in a PKD1-AKT1 heterodimer phosphorylates the AKT1 molecule within the same heterodimer."
34673053
sparser
"For instance, circ-Amotl1 is physically bound to both 3-phosphoinositide-dependent protein kinase 1 (PDK1) and AKT1, and precipitates the PDK1-dependent phosphorylation of AKT1 [ 36 ]. circ-Foxo3 can [MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
33144187
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"For instance, circ-Amotl1 is physically bound to both 3-phosphoinositide-dependent protein kinase 1 (PDK1) and AKT1, and precipitates the PDK1-dependent phosphorylation of AKT1 [ 36 ]."
33144187
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"IRS1 generates second messengers and recruits and activates phosphoinositide-dependent kinase (PDK), which in turn phosphorylates and activates protein kinase B (Akt) and protein kinase C (PKC)."
38631512