Phosphoinositide-dependent protein kinase 1, a sensor of protein conformation
Phosphoinositide-dependent protein kinase 1 (PDK1) is a protein kinase that phosphorylates and activates several other protein kinases from the AGC group (which includes PKA, PKG and PKC), to which PDK1 also belongs. Recent data suggests that PDK1 specificity is achieved by regulation of its interac …
Chain A, 3-phosphoinositide-dependent protein kinase 1 (human) | Protein Target - PubChem
Protein target information for Chain A, 3-phosphoinositide-dependent protein kinase 1 (human). Find diseases associated with this biological target and compounds tested against it in bioassay experiments.
Chain A, 3-phosphoinositide-dependent protein kinase 1 (human) | Protein Target - PubChem
Protein target information for Chain A, 3-phosphoinositide-dependent protein kinase 1 (human). Find diseases associated with this biological target and compounds tested against it in bioassay experiments.
Peroxovanadate induces tyrosine phosphorylation of phosphoinositide-dependent protein kinase-1 potential involvement of src...
TY - JOUR. T1 - Peroxovanadate induces tyrosine phosphorylation of phosphoinositide-dependent protein kinase-1 potential involvement of src kinase. AU - Grillo, S. AU - Gremeaux, T. AU - Casamayor, A. AU - Alessi, DR. AU - Le, Marchand-Brustel Y. AU - Tanti, JF.. PY - 2000/1/1. Y1 - 2000/1/1. M3 - Article. VL - 267. SP - 6642. EP - 6649. IS - 22. ER - ...
Targeting 3-phosphoinositide-dependent protein kinase 1 by N-acetyl-cysteine through activation of peroxisome proliferators...
NAC, a common dietary supplement and an antioxidant membrane-permeable metal-binding compound, has been shown to inhibit inflammatory responses, tumor growth including lung cancer [13, 14]. However, the mechanisms by which this reagent in control of NSCLC cell growth has not been well elucidated. We have found that NAC inhibited NSCLC cell proliferation through reduction of PDK1, a kinase and master regulator of a number of downstream signal cascades that are involved in suppression of apoptosis and promotion of tumor growth including lung cancer [4, 15]. High expression of PDK1 has been detected in invasive cancers including lung [5] and inhibition of PDK1 in several cancer cells results in significant cell growth inhibition [6]. These observations suggest that PDK1 can be considered as a target for therapies. This result, together with the finding that exogenous PDK1 diminishes the inhibitory effect of NAC on cell growth, indicates an important role of targeting PDK1 in mediating the ...
3-Phosphoinositide-dependent protein kinase 1 (PDK1) phosphorylates and activates the p70 S6 kinase in vivo and in vitro. -...
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Difference between revisions of User:Etienne Robillard/Notebook/DFP - OpenWetWare
doi: 10.1016/j.abb.2005.08.012, 10.1002/0471264180.or025.02 oph: A organo-phosphate (P-O) hydroxyl bound to a ketone or aldehyde. Synthetic intermediate and precursor to organo-phosphate agents known as AChE inhibitors. Reaction is catalyzed by the Organo-Phosphate Hydrolase enzyme, thus a (Mg)ATP-dependent ligase. See related DOIs above. dfp (Isoflurophate): http://www.drugbank.ca/drugs/DB00677, Wikipedia EC 3.1.8.2 (DFPase) http://www.genome.jp/dbget-bin/www_bget?ec:3.1.8.2 EC 3.1.8.1 (Parathion hydrolase) http://www.uniprot.org/uniprot/P0A433, http://www.drugbank.ca/drugs/DB02138 HMDB keywords: functionalized diphosphine, chim trills, DFP, Paraoxon Reaction type: oxidative desulfuration (BioCyc) Related: 3-phosphoinositide-dependent protein kinase 1, Serine/threonine-protein phosphatase 2A 55 kDa regulatory subunit B beta isoform Regulation of 3-Phosphoinositide-dependent Protein Kinase-1 (PDK1) by Src Involves Tyrosine Phosphorylation of PDK1 and Src Homology 2 Domain Binding ...
PDK1 in apical signaling endosomes participates in the rescue of the polarity complex atypical PKC by intermediate filaments in...
TY - JOUR. T1 - PDK1 in apical signaling endosomes participates in the rescue of the polarity complex atypical PKC by intermediate filaments in intestinal epithelia. AU - Mashukova, Anastasia. AU - Forteza, Radia. AU - Wald, Flavia A.. AU - Salas, Pedro J. PY - 2012/5/1. Y1 - 2012/5/1. N2 - Phosphorylation of the activation domain of protein kinase C (PKC) isoforms is essential to start a conformational change that results in an active catalytic domain. This activation is necessary not only for newly synthesized molecules, but also for kinase molecules that become dephosphorylated and need to be refolded and rephosphorylated. This rescuemechanism is responsible for the maintenance of the steady-state levels of atypical PKC (aPKC [PKCι/λ and ζ]) and is blocked in inflammation. Although there is consensus that phosphoinositide-dependent protein kinase 1 (PDK1) is the activating kinase for newly synthesized molecules, it is unclear what kinase performs that function during the rescue and where ...
Insulin downregulates pyruvate dehydrogenase kinase (PDK) mRNA: Potential mechanism contributing to increased lipid oxidation...
TY - JOUR. T1 - Insulin downregulates pyruvate dehydrogenase kinase (PDK) mRNA. T2 - Potential mechanism contributing to increased lipid oxidation in insulin- resistant subjects. AU - Majer, Martin. AU - Popov, Kirill M.. AU - Harris, Robert A.. AU - Bogardus, Clifton. AU - Prochazka, Michal. PY - 1998/10. Y1 - 1998/10. N2 - Oxidative metabolism of glucose is regulated by pyruvate dehydrogenase (PDH) that can be inhibited by isoforms of PDH kinase (PDK). Recently, increased PDK activity has been implicated in the pathogenesis of insulin resistance and non-insulin-dependent diabetes mellitus (NIDDM) in obese subjects. Using quantitative RT-PCR, we measured mRNA of PDK2 and PDK4 isoforms in skeletal muscle biopsies from nondiabetic Pima Indians, a population with a high prevalence of NIDDM associated with obesity. PDK2 and PDK4 mRNAs were positively correlated with fasting plasma insulin concentration, 2-h plasma insulin concentration in response to oral glucose, and percentage body fat, whereas ...
KEGG PATHWAY: Insulin signaling pathway - Homo sapiens (human)
Insulin binding to its receptor results in the tyrosine phosphorylation of insulin receptor substrates (IRS) by the insulin receptor tyrosine kinase (INSR). This allows association of IRSs with the regulatory subunit of phosphoinositide 3-kinase (PI3K). PI3K activates 3-phosphoinositide-dependent protein kinase 1 (PDK1), which activates Akt, a serine kinase. Akt in turn deactivates glycogen synthase kinase 3 (GSK-3), leading to activation of glycogen synthase (GYS) and thus glycogen synthesis. Activation of Akt also results in the translocation of GLUT4 vesicles from their intracellular pool to the plasma membrane, where they allow uptake of glucose into the cell. Akt also leads to mTOR-mediated activation of protein synthesis by eIF4 and p70S6K. The translocation of GLUT4 protein is also elicited through the CAP/Cbl/TC10 pathway, once Cbl is phosphorylated by INSR. Other signal transduction proteins interact with IRS including GRB2. GRB2 is part of the cascade including SOS, RAS, RAF and MEK ...
KEGG PATHWAY: Insulin signaling pathway - Danio rerio (zebrafish)
Insulin binding to its receptor results in the tyrosine phosphorylation of insulin receptor substrates (IRS) by the insulin receptor tyrosine kinase (INSR). This allows association of IRSs with the regulatory subunit of phosphoinositide 3-kinase (PI3K). PI3K activates 3-phosphoinositide-dependent protein kinase 1 (PDK1), which activates Akt, a serine kinase. Akt in turn deactivates glycogen synthase kinase 3 (GSK-3), leading to activation of glycogen synthase (GYS) and thus glycogen synthesis. Activation of Akt also results in the translocation of GLUT4 vesicles from their intracellular pool to the plasma membrane, where they allow uptake of glucose into the cell. Akt also leads to mTOR-mediated activation of protein synthesis by eIF4 and p70S6K. The translocation of GLUT4 protein is also elicited through the CAP/Cbl/TC10 pathway, once Cbl is phosphorylated by INSR. Other signal transduction proteins interact with IRS including GRB2. GRB2 is part of the cascade including SOS, RAS, RAF and MEK ...
Mutant PIK3CA-Bearing Colon Cancer Cells Display Increased Metastasis in an Orthotopic Model | Cancer Research
The phosphatidylinositol 3-kinases (PI3K) are a family of lipid kinases that are involved in a wide range of cancer-related signaling pathways, including proliferation, survival, motility, differentiation, cytoskeletal rearrangement, and angiogenesis ( 1- 3). PI3Ks are categorized into three families according to their subunit structure, regulation, and substrate selectivity ( 4). Class IA PI3K, which comprises a 110-kDa catalytic subunit and a regulatory subunit of 85, 55, or 50 kDa, plays an important role in regulating proliferation, motility, and survival ( 5, 6). AKT, the major downstream effector of PI3K, is activated by phosphoinositide-dependent protein kinase 1, which is recruited and phosphorylated by activation of PI3K. The PI3K/AKT signaling pathway regulates several transcriptional factors, including the forkhead transcription factor FKHR and nuclear factor-κB, which are involved in cell cycle control and apoptosis ( 7- 11). The PI3K/AKT pathway has also been reported to regulate ...
JCI - Welcome
Spermatogonial stem cells (SSCs) capable of self-renewal and differentiation are the foundation for spermatogenesis. Although several factors important for these processes have been identified, the fundamental mechanisms regulating SSC self-renewal and differentiation remain unknown. Here, we investigated a role for the Foxo transcription factors in mouse spermatogenesis and found that Foxo1 specifically marks mouse gonocytes and a subset of spermatogonia with stem cell potential. Genetic analyses showed that Foxo1 was required for both SSC homeostasis and the initiation of spermatogenesis. Combined deficiency of Foxo1, Foxo3, and Foxo4 resulted in a severe impairment of SSC self-renewal and a complete block of differentiation, indicating that Foxo3 and Foxo4, although dispensable for male fertility, contribute to SSC function. By conditional inactivation of 3-phosphoinositide-dependent protein kinase 1 (Pdk1) and phosphatase and tensin homolog (Pten) in the male germ line, we found that PI3K ...
JCI - Welcome
Spermatogonial stem cells (SSCs) capable of self-renewal and differentiation are the foundation for spermatogenesis. Although several factors important for these processes have been identified, the fundamental mechanisms regulating SSC self-renewal and differentiation remain unknown. Here, we investigated a role for the Foxo transcription factors in mouse spermatogenesis and found that Foxo1 specifically marks mouse gonocytes and a subset of spermatogonia with stem cell potential. Genetic analyses showed that Foxo1 was required for both SSC homeostasis and the initiation of spermatogenesis. Combined deficiency of Foxo1, Foxo3, and Foxo4 resulted in a severe impairment of SSC self-renewal and a complete block of differentiation, indicating that Foxo3 and Foxo4, although dispensable for male fertility, contribute to SSC function. By conditional inactivation of 3-phosphoinositide-dependent protein kinase 1 (Pdk1) and phosphatase and tensin homolog (Pten) in the male germ line, we found that PI3K ...
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Molecular association of cancer cell metastasis with signaling pathways has been explicated so as to aid in the development of new prognostic models for better cancer therapies. However, those metastatic signaling pathways are barely explored to take account of the functions of enzymes involved in cellular metabolism. Particularly, the metabolic enzymes in de novo purine biosynthesis have been overlooked for their potential roles in cancer cell metastasis even though they have been successfully validated anti-cancer drug targets. Meanwhile, several lines of recent discoveries on de novo purine biosynthesis suggest that the spatiotemporal assembly of purine biosynthetic enzymes, the purinosome, is under controls of signaling pathways in cancer cells. The results of the inquiry reveal an unanticipated mechanism of action of 3-phosphoinositide-dependent protein kinase 1 (PDK1) signaling pathways in regulation of purine biosynthesis in an Akt-independent manner. Considering the biological action of ...
Structural insights into the regulation of PDK1 by phosphoinositides and inositol phosphates<...
TY - JOUR. T1 - Structural insights into the regulation of PDK1 by phosphoinositides and inositol phosphates. AU - Komander, David. AU - Fairservice, Alison. AU - Deak, Maria. AU - Kular, Gursant S.. AU - Prescott, Alan R.. AU - Downes, C. Peter. AU - Safrany, Stephen T.. AU - Alessi, Dario R.. AU - Van Aalten, Daan M.F.. PY - 2004/10/13. Y1 - 2004/10/13. N2 - 3-phosphoinositide-dependent protein kinase-1 (PDK1) phosphorylates and activates many kinases belonging to the AGC subfamily. PDK1 possesses a C-terminal pleckstrin homology (PH) domain that interacts with PtdIns(3,4,5)P3/PtdIns(3,4)P2 and with lower affinity to PtdIns(4,5)P2. We describe the crystal structure of the PDK1 PH domain, in the absence and presence of PtdIns(3,4,5)P3 and Ins(1,3,4,5)P4. The structures reveal a budded PH domain fold, possessing an N-terminal extension forming an integral part of the overall fold, and display an unusually spacious ligand-binding site. Mutagenesis and lipid-binding studies were used to define ...
cdna definition - Natural Killer cells
The function of PI3K-mTOR pathway in regulating NK cell improvement has been extensively reported. However, it stays unclear whether or not NK cell improvement depends upon the protein kinase B (PKB), which hyperlinks PI3K and mTOR, maybe because of the potential redundancy of PKB. PKB has two phosphorylation websites, threonine 308 (T308) and serine 473 (S473), which may be phosphorylated by phosphoinositide-dependent protein kinase-1 (PDK1) and mTORC2, respectively. In this research, we established a mouse mannequin wherein PKB was inactivated by the deletion of PDK1 and Rictor, a key element of mTORC2, respectively.. We discovered that the only deletion of PDK1 or Rictor may result in a major defect in NK cell improvement, whereas mixed deletion of PDK1 and Rictor severely hindered NK cell improvement on the early stage. Notably, ectopic expression of myristoylated PKB considerably rescued this defect. In phrases of mechanism, in PDK1/Rictor-deficient NK cells, E4BP4, a transcription issue ...
culture cells definition - Natural Killer cells
The function of PI3K-mTOR pathway in regulating NK cell improvement has been extensively reported. However, it stays unclear whether or not NK cell improvement depends upon the protein kinase B (PKB), which hyperlinks PI3K and mTOR, maybe because of the potential redundancy of PKB. PKB has two phosphorylation websites, threonine 308 (T308) and serine 473 (S473), which may be phosphorylated by phosphoinositide-dependent protein kinase-1 (PDK1) and mTORC2, respectively. In this research, we established a mouse mannequin wherein PKB was inactivated by the deletion of PDK1 and Rictor, a key element of mTORC2, respectively.. We discovered that the only deletion of PDK1 or Rictor may result in a major defect in NK cell improvement, whereas mixed deletion of PDK1 and Rictor severely hindered NK cell improvement on the early stage. Notably, ectopic expression of myristoylated PKB considerably rescued this defect. In phrases of mechanism, in PDK1/Rictor-deficient NK cells, E4BP4, a transcription issue ...
The kinase DYRK1A phosphorylates the transcription factor FKHR at Ser329 in vitro, a novel in vivo phosphorylation site |...
Forkhead in rhabdomyosarcoma (FKHR) is a transcription factor that has been implicated in the control of gene expression by insulin, as well as the regulation of apoptosis by survival factors. These signals trigger the protein kinase B (PKB)-catalysed phosphorylation of FKHR at three residues (Thr24, Ser256 and Ser319) by a phosphoinositide 3-kinase-dependent pathway that results in the nuclear exit and inactivation of this transcription factor. Here, we have identified a conserved residue (Ser329) as a novel in vivo phosphorylation site on FKHR. Ser329 phosphorylation also decreases the ability of FKHR to stimulate gene transactivation and reduces the proportion of FKHR present in the nucleus. However, unlike the residues targetted by PKB, Ser329 is phosphorylated in unstimulated HEK-293cells, and phosphorylation is not increased by stimulation with insulin-like growth factor-1 or by transfection with 3-phosphoinositide-dependent protein kinase-1. We have also purified a protein kinase to near ...
RCSB PDB - 1OKZ: Structure of human PDK1 kinase domain in complex with UCN-01 Macromolecule Annotations Page
1OKZ: Structural Basis for Ucn-01 (7-Hydroxystaurosporine) Specificity and Pdk1 (3-Phosphoinositide-Dependent Protein Kinase-1) Inhibition
RCSB PDB for 1OKY
1OKY: Structural Basis for Ucn-01 (7-Hydroxystaurosporine) Specificity and Pdk1 (3-Phosphoinositide-Dependent Protein Kinase-1) Inhibition
GENTAUR antibody-antibodies.com The Marketplace for Antibodies : 3-Phosphoinositide-dependent PDK1 negatively regulates...
antibody-antibodies.com is the marketplace for research antibodies. Find the right antibody for your research needs. 3-Phosphoinositide-dependent PDK1 negatively regulates transforming growth factor-beta-induced signaling in a kinase-dependent manner through physical interaction with Smad proteins.
Acute regulation of PDK1 by a complex interplay of molecular switches | Biochemical Society Transactions | Portland Press
Phosphoinositide-dependent kinase 1 (PDK1) is the master regulator of at least 23 other AGC kinases whose downstream signalling has often been implicated in various diseases and in particular in cancer. Therefore there has been great interest in determining how PDK1 is controlled and how it regulates its substrates spatially and temporally. The understanding of these mechanisms could offer new possibilities for therapeutic intervention. Over the years, a more comprehensive view of the mechanisms involved in the regulation of PDK1 has emerged and these comprise serine/threonine as well as tyrosine phosphorylation, subcellular localization, regulator binding and conformation status. In the present review, we discuss how various molecular mechanisms are together responsible for the conformational regulation behind the activation of PDK1 in cells. ...
Phosphatidylinositol (PI) 3-kinase mediates multiple pathways that regulate many aspects of - Structure of Rhomboid Protease in...
Phosphatidylinositol (PI) 3-kinase mediates multiple pathways that regulate many aspects of the cell including rate of metabolism, survival, migration, and proliferation. apoptosis, suggesting that FLII itself is also a survival element. These findings support the model that CISK phosphorylates FLII and activates nuclear receptor transcription and suggest a new cell survival signaling pathway mediated by PI 3-kinase and CISK. Cell death and survival are tightly controlled throughout development, through the action of numerous factors and pathways (1C6). Of these, PI2 3-kinase and its own downstream effectors are being among the most studied widely. PI 3-kinase pathway is vital for success and proliferation of mammalian cells and continues to be implicated in cancers (7C10). Through the legislation of D3-phosphoinositol amounts in cells, PI 3-kinases control the experience of 3-phosphoinositide-dependent kinase and associates from the AGC (cAMP-dependent proteins kinase/proteins kinase G/proteins ...
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G-protein-coupled receptors (GPCRs) activate the epidermal growth factor receptor (EGFR) and mediate EGFR-independent signaling pathways to promote the growth of a variety of cancers including head and neck squamous cell carcinoma (HNSCC). Identification of the common signaling mechanisms involved in GPCR-induced EGFR-dependent and independent processes will facilitate the development of more therapeutic strategies. In this study, we hypothesized that phosphoinositide-dependent kinase 1 (PDK1) contributes to GPCR-EGFR crosstalk and signaling in the absence of EGFR and suggests that inhibition of the PDK1 pathway may be effective in the treatment of HNSCC. The contribution of PDK1 to the EGFR-dependent and independent signaling in HNSCC was determined using RNAi, a kinase-dead mutant and pharmacological inhibition. In vivo xenografts studies were also performed to determine the efficacy of targeting PDK1 alone or in combination with the FDA-approved EGFR inhibitor cetuximab. PDK1 contributed to ...
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Aberrant activation of the intracellular PI3K-AKT-mTOR signaling pathway, which regulates critical processes such as cell cycle and survival, is one of the most common occurrences in human cancers and has been the focus of targeted therapy development. However, inhibitors targeting PI3K, AKT, or mTOR have shown limited clinical benefit. To identify new regulators of the PI3K-AKT pathway, Wheeler and colleagues screened 7,450 shRNAs for kinases or GTPases that affect AKT phosphorylation at serine 473 (S473), and identified 29 genes that had not been previously implicated in PI3K-AKT signaling, as well as genes known to regulate AKT phosphorylation. Of the 29 genes, the most-represented functional group was the RAB GTPases, which regulate endomembrane trafficking. Knockdown of RAB35, one of the five RAB GTPases identified in the screen, in multiple cell lines resulted in decreased AKT phosphorylation at S473 as well as diminished phosphorylation of phosphoinositide-dependent kinase 1 (PDK1) and ...
Mutation of SAC1, an Arabidopsis SAC Domain Phosphoinositide Phosphatase, Causes Alterations in Cell Morphogenesis, Cell Wall...
Phosphoinositides have traditionally been known to be important in the generation of the second messengers inositol 1,4,5,-triphosphate and diacylglycerol. Recently, it was demonstrated that in yeast and animals, phosphoinositides themselves are regulators of a wide variety of cellular processes, such as signal transduction, actin cytoskeleton organization, vesicle trafficking, and activation of proteins such as phosphoinositide-dependent kinase 1 and phospholipase D (Martin, 1998; Takenawa and Itoh, 2001). In plant cells, all phosphoinositide forms except phosphatidylinositol 3,4,5-triphosphate [PtdIns(3,4,5)P3] have been identified, and they have been suggested to play important roles in vesicle trafficking (Matsuoka et al., 1995; Kim et al., 2001), pollen tube growth (Kost et al., 1999), and stress and hormone responses (Mikami et al., 1998; Meijer et al., 1999, 2001; Pical et al., 1999; DeWald et al., 2001). PtdIns(4,5)P2 has been shown to bind profilin (Kovar et al., 2001) and to regulate ...
An inhibitor of mTOR reduces neoplasia and normalizes p70/S6 kinase activity in Pten+/− mice | PNAS
It is likely that the loss of Pten found in the tumors of PTEN+/− mice leads to increased levels of PtdIns(3,4,5)P3, which in turn is able to activate AKT, 3-phosphoinositide-dependent kinase 1, S6K, mTOR, and many other proteins. In combination, these activated proteins probably contribute to the transformation and increased tumor proliferation that was observed in a variety of organs (Figs. 1 and 2). Of these activated proteins, S6K is likely to play a major role in the progression of the cell cycle into the S phase. Microinjection of anti-S6K antibodies into quiescent rat embryo fibroblasts prevents the mitogenic effect of serum (32, 33). In T cells, which are unable to proliferate in the presence of rapamycin, a rapamycin-resistant allele of S6K is sufficient to rescue the activation of an E2F reporter (42). S6K1−/− mouse embryonic stem cells have an elevated proportion of cells in G0/G1 and slower proliferation relative to wild type (10). Finally, dTOR mutation is associated with ...
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An understanding of the molecular basis for the survival of tumor cells through resistance to apoptosis is critical for the development of rational and suitably targeted antineoplastic therapies. An increasing number of studies have shown that activation of the PI3-K/Akt survival pathway plays an important role in BCR-ABL-mediated leukemogenesis. More recently, the significance of Akt activation in CML was investigated in the context of imatinib resistance. Interestingly, whereas the BCR-ABL T315I imatinib-resistant mutation is refractory to the combination of imatinib and numerous compounds, inhibition of Akt signaling with a phosphoinositide-dependent kinase-1 inhibitor, OSU-03012, synergizes with imatinib to induce apoptosis in BCR-ABL T315I cells ( 46). These studies suggest that Akt activation is an important event even in imatinib-resistant CML.. The FoxO3a transcription factor represents a critical substrate that is inhibited by Akt during growth factor-induced survival ( 25). We and ...
Dynamics of Phosphoinositide-Dependent Signaling in Sympathetic Neurons
Phosphatidylinositol 4,5-bisphosphate [PI(4,5)P2] is a minor phospholipid in the cytoplasmic leaflet of the plasma membrane. Depletion of PI(4,5)P2 via phospholipase C-mediated hydrolysis leads to a decrease in exocytosis and alters electrical excitability in neurons. Restoration of PI(4,5)P2 is ess …
PDHK | 丙酮酸脱氢酶激酶 | 抑制剂 | MCE
PS10 是一种新型,有效且具有 ATP 竞争性的广谱 PDK 抑制剂,可抑制所有 PDK 同工型,对 PDK2,PDK4,PDK1 和 PDK3 的 IC50 分别为 0.8 μM,0.76 μM,2.1 μM 和 21.3 μM。 PS10 对 PDK2 (Kd= 239 nM) 的亲和力高于对 Hsp90 (Kd= 47 μM)。 PS10 改善葡萄糖耐量,刺激饮食引起的肥胖症中的心肌碳水化合物氧化。 PS10 具有研究糖尿病性心肌病的潜力 ...
The Akt activation inhibitor TCN-P inhibits Akt phosphorylation by binding to the PH domain of Akt and blocking its recruitment...
Persistently hyperphosphorylated Akt contributes to human oncogenesis and resistance to therapy. Triciribine (TCN) phosphate (TCN-P), the active metabolite of the Akt phosphorylation inhibitor TCN, is in clinical trials, but the mechanism by which TCN-P inhibits Akt phosphorylation is unknown. Here we show that in vitro, TCN-P inhibits neither Akt activity nor the phosphorylation of Akt S473 and T308 by mammalian target of rapamycin or phosphoinositide-dependent kinase 1. However, in intact cells, TCN inhibits EGF-stimulated Akt recruitment to the plasma membrane and phosphorylation of Akt. Surface plasmon resonance shows that TCN, but not TCN, binds Akt-derived pleckstrin homology (PH) domain (K(D) 690 nM). Furthermore, nuclear magnetic resonance spectroscopy shows that TCN-P, but not TCN, binds to the PH domain in the vicinity of the PIP3-binding pocket. Finally, constitutively active Akt mutants, Akt1-T308D/S473D and myr-Akt1, but not the transforming mutant Akt1-E17K, are resistant to TCN ...
Growth signalling pathways in Ara... preview & related info | Mendeley
(2003) Bögre et al. Trends in Plant Science. Lipid-derived signals are central to regulating a multitude of cellular processes but, in plants, little is known of the downstream signalling pathways. The Arabidopsis 3-phosphoinositide-dependent...
Metabolic Disorder
Macrophage polarization is a process by which macrophages carry out various functional programs responding to signals. Pyruvate Dehydrogenase Kinase (PDK) is a kinase, phosphorylates pyruvate dehydrogenase with ATP to cause…. Read More Read More. ...
Agc 017 | Alomone Labs | Bioz
Bioz Stars score, Techniques, Protocol Conditions and more for Agc 017, supplied by Alomone Labs. Data for Agc 017 gathered from related PubMed articles.
PDK1-Foxo1 in agouti-related peptide neurons regulates energy homeostasis by modulating food intake and energy expenditure<...
TY - JOUR. T1 - PDK1-Foxo1 in agouti-related peptide neurons regulates energy homeostasis by modulating food intake and energy expenditure. AU - Cao, Yongheng. AU - Nakata, Masanori. AU - Okamoto, Shiki. AU - Takano, Eisuke. AU - Yada, Toshihiko. AU - Minokoshi, Yasuhiko. AU - Hirata, Yukio. AU - Nakajima, Kazunori. AU - Iskandar, Kristy. AU - Hayashi, Yoshitake. AU - Ogawa, Wataru. AU - Barsh, Gregory S.. AU - Hosoda, Hiroshi. AU - Kangawa, Kenji. AU - Itoh, Hiroshi. AU - Noda, Tetsuo. AU - Kasuga, Masato. AU - Nakae, Jun. N1 - Copyright: Copyright 2011 Elsevier B.V., All rights reserved.. PY - 2011. Y1 - 2011. N2 - Insulin and leptin intracellular signaling pathways converge and act synergistically on the hypothalamic phosphatidylinositol-3-OH kinase/3-phosphoinositide-dependent protein kinase 1 (PDK1). However, little is known about whether PDK1 in agouti-related peptide (AGRP) neurons contributes to energy homeostasis. We generated AGRP neuron-specific PDK1 knockout (AGRPPdk1-/-) mice and ...
JCI - Administration of BMP2/7 in utero partially reverses Rubinstein-Taybi syndrome-like skeletal defects induced by Pdk1 or...
Mutations in the coactivator CREB-binding protein (CBP) are a major cause of the human skeletal dysplasia Rubinstein-Taybi syndrome (RTS); however, the mechanism by which these mutations affect skeletal mineralization and patterning is unknown. Here, we report the identification of 3-phosphoinositide-dependent kinase 1 (PDK1) as a key regulator of CBP activity and demonstrate that its functions map to both osteoprogenitor cells and mature osteoblasts. In osteoblasts, PDK1 activated the CREB/CBP complex, which in turn controlled runt-related transcription factor 2 (RUNX2) activation and expression of bone morphogenetic protein 2 (BMP2). These pathways also operated in vivo, as evidenced by recapitulation of RTS spectrum phenotypes with osteoblast-specific Pdk1 deletion in mice (Pdk1osx mice) and by the genetic interactions observed in mice heterozygous for both osteoblast-specific Pdk1 deletion and either Runx2 or Creb deletion. Finally, treatment of Pdk1osx and Cbp+/- embryos with BMPs in utero ...
Inactivation of the Akt Survival Pathway during Photoreceptor Apoptosis in the Retinal Degeneration Mouse | IOVS | ARVO Journals
We first evaluated the phosphorylation state of Akt at Ser-473, the site of phosphorylation by MAPKAPK-2, which has been shown to be critical for the generation of high levels of Akt enzyme activity. 15 32 33 Several other kinases have also been reported to phosphorylate Akt at Ser-473, including integrin-linked kinase (ILK), 34 35 36 3-phosphoinositide-dependent kinase-1 (PDK-1) 35 and DNA-dependent protein kinase (DNA-PK). 37 Our data showed two distinct phases of Ser-473 Akt modulation during photoreceptor degeneration: the first one was characterized by the inactivation of Akt, and extended from early onset (13 days) to the peak of photoreceptor apoptosis (15 days), and the following one displayed a striking Akt activation during the period when most photoreceptors have degenerated. The fact that Akt activation levels were decreased and no immunoreactivity of the active form was detected at the photoreceptor level, strongly suggests that the Akt survival signaling pathway was inhibited ...
AMP activated protein kinase-α2 regulates expression of estrogen-related receptor-α, a metabolic transcription factor related...
Hu X, Xu X, Lu Z, Zhang P, Fassett J, Zhang Y, Xin Y, Hall JL, Viollet B, Bache RJ, et al. AMP activated protein kinase-α2 regulates expression of estrogen-related receptor-α, a metabolic transcription factor related to heart failure development. Hypertension [Internet]. 2011;(4):696-703.
CMPD-1 | ≥99%(HPLC) | p38 MAPK Inhibitor | AdooQ®
CMPD-1 is a non-ATP-competitive, selective inhibitor of p38α-mediated MK2a (mitogen-activated protein kinase-2a) phosphorylation (apparent Ki = 330 nM).
OriGene - Pdpk1 (NM 031081) cDNA Clone
Pdpk1 - Pdpk1 (untagged ORF) - Rat 3-phosphoinositide dependent protein kinase-1 (Pdpk1), (10 ug) available for purchase from OriGene - Your Gene Company.
APExBIO - GSK690693|Pan-AKT inhibitor,ATP-competitive and potent|CAS# 937174-76-0
GSK690693 is a pan-Akt inhibitor targeting Akt1, 2, 3 with IC50 values of 2, 13 and 9 nM, respectively [1, 2]. In addition, it also inhibits AMPK (IC50=50 nM), DAPK3 (IC50=81 nM), PAK4, 5, and 6 (IC50=10, 52, 6 nM), as well as the members of AGC kinase fa
PKB - Bing 词典
必应词典为您提供PKB的释义,网络释义: 民族觉醒党(PARTAI KEBANGKITAN BANGSA);PACAMOR KUBAR BEARINGS;复兴党;
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Mass Spectrometry-based Label-free Quantitative Proteomic Analysis of CCl4-induced Acute Liver Injury in Mice Intervened by...
Title:Mass Spectrometry-based Label-free Quantitative Proteomic Analysis of CCl4-induced Acute Liver Injury in Mice Intervened by Total Glycosides from Ligustri Lucidi Fructus. VOLUME: 17 Author(s):Qian Lu, Hai-Zhu Xing and Nian-Yun Yang*. Affiliation:Jiangsu Collaborative Innovation Center of Chinese Medicinal Resources Industrialization, Jiangsu Plant Medicine Research and Development Center, Nanjing University of Chinese Medicine, Nanjing 210023, Jiangsu Collaborative Innovation Center of Chinese Medicinal Resources Industrialization, Jiangsu Plant Medicine Research and Development Center, Nanjing University of Chinese Medicine, Nanjing 210023, Jiangsu Collaborative Innovation Center of Chinese Medicinal Resources Industrialization, Jiangsu Plant Medicine Research and Development Center, Nanjing University of Chinese Medicine, Nanjing 210023. Keywords:Ligustri Lucidi Fructus, Proteome, 3-Phosphoinositide-dependent protein kinase 1, Insulin-Like growth factor 1, Autophagy ...
Parathyroid hormone-related protein induces cell survival in human renal cell carcinoma through the PI3K Akt pathway: evidence...
We have recently shown that parathyroid hormone-related protein (PTHrP), a cytokine-like polyprotein, is critical for human renal cell carcinoma (RCC) growth by inhibiting tumor cell apoptosis. Here, we have explored mechanisms by which PTHrP controls tumor cell survival. Using specific inhibitors of phosphoinositide 3-kinase (PI3K) and depletion of Akt kinase by RNA interference, we established that PTHrP is one of the main factor involved in the constitutive activation of this pathway in human RCC, independently of von Hippel-Lindau (VHL) tumor suppressor gene expression. Interestingly, PTHrP induced phosphorylation of Akt at S473 but had no influence on phosphorylation at T308. Through transfection with integrin-linked kinase (ILK) constructs and RNA interference, we provide evidence that ILK is involved in human RCC cell survival. PTHrP activates ILK which then acts as a phosphoinositide-dependent kinase (PDK)-2 or a facilitator protein to phosphorylate Akt at S473. Among other kinases ...
High-Resolution Structure of the Pleckstrin Homology Domain of Protein Kinase B/Akt Bound to Phosphatidylinositol (3,4,5)...
TY - JOUR. T1 - High-Resolution Structure of the Pleckstrin Homology Domain of Protein Kinase B/Akt Bound to Phosphatidylinositol (3,4,5)-Trisphosphate. AU - Thomas, Christine C.. AU - Deak, Maria. AU - Alessi, Dario R.. AU - van Aalten, Daan M. F.. PY - 2002/7/23. Y1 - 2002/7/23. N2 - The products of PI 3-kinase activation, PtdIns(3,4,5)P3 and its immediate breakdown product PtdIns(3,4)P2, trigger physiological processes, by interacting with proteins possessing pleckstrin homology (PH) domains [1, 2]. One of the best characterized PtdIns(3,4,5)P3/PtdIns(3,4)P2 effector proteins is protein kinase B (PKB), also known as Akt [3-5]. PKB possesses a PH domain located at its N terminus, and this domain binds specifically to PtdIns(3,4,5)P3 and PtdIns(3,4)P2 with similar affinity [6, 7]. Following activation of PI 3-kinase, PKB is recruited to the plasma membrane by virtue of its interaction with PtdIns(3,4,5)P3/PtdIns(3,4)P2 [8-10]. PKB is then activated by the 3-phosphoinositide-dependent pro-tein ...
PDK - Portal Development Kit in Computing & IT by AcronymsAndSlang.com
What does Computing & IT PDK stand for? Hop on to get the meaning of PDK. The Computing & IT Acronym /Abbreviation/Slang PDK means Portal Development Kit. by AcronymAndSlang.com
YKR051W - PrimePCR Assay and Template | Life Science | Bio-Rad
Use Bio-Rads PrimePCR assays, controls, templates for your target gene. Every primer pair is optimized, experimentally validated, and performance guaranteed.
PDK SELAYANG / CBR SELAYANG: Prof Dr Zaleha appointed as IIUM Rector
PDK Selayang (Pusat Pemulihan Dalam Komuniti Selayang) telah ditubuhkan pada 1hb Sept 1991, oleh sekumpulan ibubapa kepada kanak-kanak kurang upaya (pada masa tersebut dipanggil sebagai kanak-kanak istimewa) yang anak-anak mereka telah dikeluarkan dari pembelajaran wajib di sekolah-sekolah aliran perdana di Selayang, dengan alasan mereka (OKU tersebut) tidak boleh belajar. Alasan sebenar Guru Besar sekolah-sekolah tersebut ialah mereka takut graf pencapaian sekolah akan menurun ...
Fakultas Ilmu Pendidikan | Profesi Online
PROFESI-UNM.COM - Himpunan Mahasiswa Jurusan (HMJ) Pendidikan Khusus (PKh) Fakultas Ilmu Pengetahuan Universitas Negeri Makassar (FIP-UNM) gelar bakti sosial dengan tema Menjalin ...