Phosphoinositide dependent protein kinase. Medical search. Frequent questions

Here we present a systematic approach to targeting a functionally conserved allosteric site on the protein kinase PDK1 called the PDK1-interacting fragment (PIF)tide-binding site, or PIF pocket. (rcsb.org)
More than two dozen prosurvival and progrowth kinases dock a conserved peptide tail into this binding site, which recruits them to PDK1 to become activated. (rcsb.org)
These allosteric small molecules are substrate-selective PDK1 inhibitors when used as single agents, but when combined with an ATP-competitive inhibitor, they completely suppress the activation of the downstream kinases. (rcsb.org)
Akt isoenzymes (Akt1-3) are downstream of IRK and are activated by phosphatidylinositol-dependent kinase 1 (PDK1) phosphorylating T(308) before S(473) autophosphorylation. (nih.gov)
1. Phosphoinositide-dependent protein kinase 1 (PDK1) mediates potent inhibitory effects on eosinophils. (nih.gov)
3. Prostaglandin E2 stimulates normal bronchial epithelial cell growth through induction of c-Jun and PDK1, a kinase implicated in oncogenesis. (nih.gov)
Sugyun An et al, Inhibition of 3-phosphoinositide-dependent protein kinase 1 (PDK1) can revert cellular senescence in human dermal fibroblasts, Proceedings of the National Academy of Sciences (2020). (phys.org)
Phosphatidylinositol [PI] 3,4,5 triphosphate [P3] allows for the recruitment of phospholipid effectors, including the central mediators of the PI3K pathway , AKT and PDK1 (3-phosphoinositide-dependent protein kinase-1). (medscape.com)
p70S6K activation requires sequential phosphorylations at proline-directed residues in the putative autoinhibitory pseudosubstrate domain, as well asT389, a site phosphorylated by phosphoinositide-dependent kinase 1 (PDK1). (rndsystems.com)
Serine/Threonine Kinases (STKs), Phosphoinositide-dependent kinase 1 (PDK1) subfamily, catalytic (c) domain. (umbc.edu)
The PDK1 subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase (PI3K). (umbc.edu)
PDK1 carries an N-terminal catalytic domain and a C-terminal pleckstrin homology (PH) domain that binds phosphoinositides. (umbc.edu)
Thr308 phosphorylation, but not Ser473 phosphorylation, requires the yeast orthologues of mammalian PDK1 (3-phosphoinositide-dependent protein kinase-1): Pkh1 and Pkh2. (neighborhoodhousecharterschool.org)

The dynamics of both follicular reserves appears to result from the fine tuning of regulations involving two main pathways, the phosphatase and tensin homolog (PTEN)/phosphatidylinositol-3 kinase (PI3K)/3-phosphoinositide-dependent protein kinase-1 (PDPK1)/v-akt murine thymoma viral oncogene homolog 1 (AKT1) and the bone morphogenetic protein (BMP)/anti-Müllerian hormone (AMH)/SMAD signaling pathways. (bioone.org)
As a potential molecular link, CD133-mediated activation of phosphoinositide 3-kinase/serine-threonine kinase (PI3K/AKT) signaling appears to increase the NRF2 protein levels via phosphorylation and the consequent inhibition of glycogen synthase kinase (GSK)-3β. (frontiersin.org)
Phosphoinositide 3-kinase (PI3K) takes a key role in a plethora of physiologic processes and controls cell growth, metabolism, immunity, cardiovascular and neurological function, and more. (chimia.ch)
The discovery of wortmannin as the first potent PI3K inhibitor (PI3Ki) in the 1990s provided rapid identification of PI3K-dependent processes, which drove the assembly of the PI3K/protein kinase B (PKB/Akt)/target of rapamycin (mTOR) pathway. (chimia.ch)
AKT is activated by phosphatidylinositol 3-phosphate (PIP3), which is produced by PI(3)kinases (PI3K). (nih.gov)
mTOR (mammalian target of rapamycin) is downstream of AKT in the phosphatidylinositol-3-kinase (PI3K)/AKT/mTOR pathway . (medscape.com)
It phosphorylates the activation loop of AGC kinases that are regulated by PI3K such as PKB, SGK, and PKC, among others, and is crucial for their activation. (umbc.edu)
Furthermore, it was found that beclin‑1 and class III phosphoinositide 3 kinase (PI3K) levels were increased, while levels of the anti‑apoptotic protein B‑cell lymphoma 2 (Bcl‑2) were decreased after Cd treatment. (spandidos-publications.com)
The phosphatidylinositol 3-kinase (PI3K)/protein kinase B (AKT)/mammalian target of rapamycin (mTOR) pathway is a central oncogenic pathway deregulated in cancer. (gabapathway.com)
PI3K kinases function as key signal transducers downstream of cell-surface receptors and key regulators of cell survival and metabolism (7). (gabapathway.com)
The PI3K kinase family comprises 8 enzymes organized into 3 classes (I-III) based on sequence homology. (gabapathway.com)

Ras-mediated activation of DH-PH-Sos did not require activation of mitogen-activated protein kinase but it was dependent on activation of phosphoinositide 3-kinase. (embl.de)
Has a critical role in the stimulation of the CDK20/MAPK3 mitogen-activated protein kinase cascade by epidermal growth factor. (drugbank.com)
Interestingly, protein microarray analysis suggested that TGFβ1/BMP9-dependent osteogenesis of C3H10T1/2 cells seemed to involve several non-canonical signaling pathways such as Janus kinase-signal transducer and activator of transcription, phosphoinositide-3-kinase-protein kinase B, and mitogen-activated protein kinase. (medsci.org)
These changes are controlled by a network of mitogen-activated protein kinase, cyclic nucleotide, calcium, and phosphoinositide-dependent intracellular signaling pathways [ 1 ]. (biomedcentral.com)

There is great interest in developing selective protein kinase inhibitors by targeting allosteric sites, but these sites often involve protein-protein or protein-peptide interfaces that are very challenging to target with small molecules. (rcsb.org)
To identify the intracellular signaling molecules that mediate the P2X4-dependent inhibition of TRPM6, the cells were treated with inhibitors of protein kinase c, protein kinase a, and phosphoinositide 3-kinase. (nih.gov)
Moreover, migration of neutrophils induced by heme was abolished by pretreatment with pertussis toxin, an inhibitor of Gα inhibitory protein, and with inhibitors of phosphoinositide 3-kinase, phospholipase Cβ, mitogen-activated protein kinases, or Rho kinase. (neuroprobe.com)
Currently, in the absence of visceral crisis, the standard of care for these patients is an endocrine therapy (ET) and cyclin-dependent kinase 4 and 6 inhibitors (CDKi) combination (4). (gabapathway.com)

hBVR activates phosphorylation of Akt1 at S(473) independent of hBVR's kinase competency. (nih.gov)
18. Prostaglandin E2-stimulated prostanoid EP4 receptors induce prolonged de novo prostaglandin E2 synthesis through biphasic phosphorylation of extracellular signal-regulated kinases mediated by activation of protein kinase A in HCA-7 human colon cancer cells. (nih.gov)
Interestingly, it was found that Src, Syk, IRAK1, and IRAK4 responsible for NF- κ B and AP-1 activation were identified as the direct molecular targets of KF by kinase enzyme assays and by measuring their phosphorylation patterns. (hindawi.com)
When cells adhere via focal adhesions to the extracellular matrix, signals are transmitted by integrins into the cell resulting in tyrosine phosphorylation of a number of focal adhesion proteins, including PTK2/FAK1 and paxillin (PXN). (drugbank.com)
p70 S6 Kinase (p70S6K) is responsible for the phosphorylation of 40S ribosomal protein S6 and is ubiquitously expressed in human adult tissues (1). (rndsystems.com)

AKT2 is a phosphoinositide-dependent serine/threonine protein kinase that is enriched in insulin responsive tissues and has been implicated in the metabolic actions of the hormone. (thermofisher.com)
Highly conserved protein-serine threonine kinases that phosphorylate and activate a group of AGC protein kinases, especially in response to the production of the SECOND MESSENGERS , phosphatidylinositol 3,4,-biphosphate (PtdIns(3,4)P2) and phosphatidylinositol 3,4,5-triphosphate (PtdIns(3,4,5)P3). (bvsalud.org)
Catalytic domain of the Protein Serine/Threonine Kinase, Phosphoinositide-dependent kinase 1. (umbc.edu)
STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. (umbc.edu)
Catalytic domain of Cyclin-Dependent protein Kinase-like Serine/Threonine Kinases. (umbc.edu)

Interaction of human biliverdin reductase with Akt/protein kinase B and phosphatidylinositol-dependent kinase 1 regulates glycogen synthase kinase 3 activity: a novel mechanism of Akt activation. (nih.gov)
PDPK1 also phosphorylates Protein Kinase B (PKB) at threonine 308 in the presence of phosphatidylinositol-3,4,5-trisphosphate. (thermofisher.com)
Akt is involved in many cellular signaling pathways and acts as a transducer of many functions initiated by growth factor receptors that activate phosphatidylinositol 3-kinase (PI 3-kinase). (thermofisher.com)
After homogenization, the samples were submitted to differential centrifugation to obtain cell membranes and, further, to phospholipase C (PIPLC) treatment, to remove membrane-bound proteins anchored by phosphatidylinositol. (bvsalud.org)
We found that it is a phosphatidylinositol (3,4,5)-trisphosphate-dependent Arf6 GAP that binds RhoA-GTP but lacks RhoGAP activity. (biologists.com)

14. Preclinical validation of 3-phosphoinositide-dependent protein kinase 1 inhibition in pancreatic cancer. (nih.gov)
PMA did not inhibit (and in fact augmented at early time points) formation of [32P] phosphatidic acid in response to fMLP, indicating that the increase in DG was not due to inhibition of cellular diglyceride kinase. (eurekamag.com)
Increased DG and inhibition of activation by sphinganine are consistent with a role for protein kinase C in activation of the respiratory burst in PMA-primed neutrophils. (eurekamag.com)
The inhibition was dependent on the activity of P2X4, since a P2X4 mutant with altered ATP sensitivity was not able to inhibit TRPM6. (nih.gov)
Inhibition of CDK5 kinase activity using a CDK5 dominant-negative mutant or the drug roscovitine significantly decreased the migration and invasion of pancreatic cancer cells in vitro. (nih.gov)
Inhibition of the signaling cascade downstream of mutant K-Ras (G12D) that involves mitogen-activated protein/extracellular signal-regulated kinase, phosphoinositide 3-kinase, or CDK5 decreased p25 protein levels. (nih.gov)
The inhibition of myocyte hypertrophy by CIP4 small interfering oligonucleotides (siRNA) was rescued by expression of a recombinant CIP4 protein, but not by a mutant lacking the N-terminal FCH domain responsible for CIP4 intracellular localization. (biomedcentral.com)

What pathways are this gene/protein implicaed in? (cancerindex.org)
Gallic acid inhibits migration and invasion in human osteosarcoma U-2 OS cells through suppressing the matrix metalloproteinase-2/-9, protein kinase B (PKB) and PKC signaling pathways. (uni-muenster.de)

Ras proteins are membrane-associated molecular switches that bind GTP and GDP and slowly hydrolyze GTP to GDP [ ( PUBMED:1898771 ) ] in fundamental events such as signal transduction, cytoskeleton dynamics and intracellular trafficking. (embl.de)

Results: Digitoxin and D6MA induced a decrease in matrix metalloproteinases expression via altered focal adhesion signaling and a suppression of the phosphoinositide 3-kinases / protein kinase B pathway which lead to enhanced adhesion, altered elasticity, and reduced motility of NSCLCs. (cdc.gov)

Both FDA-approved and investigational drugs such as imatinib, cabozantinib, dasatinib, lucitanib, and sunitinib (inhibits kinases and/or VEGFR, FGFR, PDGFR) are being evaluated in TNBC patients [ 107-111 ] and could be of value in QNBCs as well. (medscape.com)
Phorbol myristate acetate (PMA) augments chemoattractant-induced diglyceride generation in human neutrophils but inhibits phosphoinositide hydrolysis. (eurekamag.com)

[ 104 ] C-Kit is a receptor tyrosine kinase (RTK), and an increased gene copy number has been linked to an aggressive phenotype and unfavorable prognosis in TNBC. (medscape.com)

In the field of biochemistry, PDPK1 refers to the protein 3-phosphoinositide-dependent protein kinase-1, an enzyme which is encoded by the PDPK1 gene in humans. (wikipedia.org)
PDPK1 is a master kinase, which is crucial for the activation of AKT/PKB and many other AGC kinases including PKC, S6K, SGK. (wikipedia.org)
PDPK1 stands for 3-phosphoinositide-dependent protein kinase 1. (wikipedia.org)
Several PDPK1 substrates including S6K and Protein kinase C, require the binding at this docking site. (wikipedia.org)
PDPK1 is constitutively active and at present, there is no known inhibitor proteins for PDPK1. (wikipedia.org)
The activation of PDPK1's main effector, AKT, is believed to require a proper orientation of the kinase and PH domains of PDPK1 and AKT at the membrane. (wikipedia.org)
In this study, we performed a genome-wide CRISPR-Cas9-based screen and demonstrated that loss of phosphoinositide-dependent kinase-1 (PDPK1) enhances the efficacy of MEKi. (nih.gov)
PDPK1 (3 Phosphoinositide Dependent Protein Kinase 1) phosphorylates AGC kinases. (thermofisher.com)

When AKT is phosphorylated , it activates downstream kinases, including the mTOR complex, promoting protein synthesis and the growth, survival, and motility of cells. (medscape.com)

In addition to phosphorylating focal adhesion proteins, SRC is also active at the sites of cell-cell contact adherens junctions and phosphorylates substrates such as beta-catenin (CTNNB1), delta-catenin (CTNND1), and plakoglobin (JUP). (drugbank.com)
SRC is implicated in regulation of pre-mRNA-processing and phosphorylates RNA-binding proteins such as KHDRBS1. (drugbank.com)

Considering that heme induces neutrophil chemotaxis, we hypothesize that heme activates a G protein-coupled receptor. (neuroprobe.com)

Both AKT and 3 phosphoinositide dependent protein kinase contain a pleckstrin homology PH domain which will bind to PIP3 at the cell membrane, bringing the two kinases into close association with the plasma membrane and, hence, each other. (gyanin.academy)

Increased levels of CDK5, p35, and p39 protein were observed in several pancreatic cancer cell lines. (nih.gov)

Cyclin-dependent kinase 5 is amplified and overexpressed in pancreatic cancer and activated by mutant K-Ras. (nih.gov)

These genes encode leucine zipper proteins that can dimerize with proteins of the JUN family, thereby forming the transcription factor complex AP-1. (cancerindex.org)
From experimentally validated target genes of these 86 miRNAs, pan-sensitive and pan-resistant genes with concordant mRNA and protein expression associated with in-vitro drug response to 19 NCCN-recommended breast cancer drugs were selected. (cdc.gov)
The mRNA and protein expression of the 26 genes was associated with sensitivity or resistance to 18 NCCN-recommended drugs for treating breast cancer. (cdc.gov)
This domain occurred 451 times on human genes ( 1035 proteins). (umbc.edu)
This domain occurred 449 times on human genes ( 1031 proteins). (umbc.edu)

The distal intracellular signaling systems on-line after the mechanoreceptor is activated are reviewed, including those emanating from G-proteins (e.g., intracellular calcium shifts), MAPKs, and nitric oxide. (scite.ai)

Non-receptor protein tyrosine kinase which is activated following engagement of many different classes of cellular receptors including immune response receptors, integrins and other adhesion receptors, receptor protein tyrosine kinases, G protein-coupled receptors as well as cytokine receptors. (drugbank.com)
SRC appears to be one of the primary kinases activated following engagement of receptors and plays a role in the activation of other protein tyrosine kinase (PTK) families. (drugbank.com)
CIP4 is a scaffold protein that regulates membrane deformation and tubulation, organization of the actin cytoskeleton, endocytosis of growth factor receptors, and vesicle trafficking. (biomedcentral.com)

PVDF membrane was probed with 0.25 µg/mL Human/Mouse/Rat p70 S6 Kinase Monoclonal Antibody (Catalog # MAB8962) followed by HRP-conjugated Anti-Mouse IgG Secondary Antibody (Catalog # HAF007 ). (rndsystems.com)
The identity of the mechanoreceptor(s) is approached, with consideration of ion channels, integrins, connexins, the lipid membrane including caveolar and noncaveolar lipid rafts and the possibility that altering cell shape at the membrane or cytoskeleton alters integral signaling protein associations. (scite.ai)
BPH-176-3723-s003.tif (826K) GUID:?ED3A9AF4-8F71-43BE-95F4-4D75AC523BD0 Body S4.Development of TRPC3\Nox2 proteins complex on the plasma membrane. (enmd-2076.com)

We initially examined the effect of sphinganine, an inhibitor of protein kinase C (Ca2+/phospholipid-dependent enzyme), on activation of primed neutrophils. (eurekamag.com)
Inflammasome activation and pyroptosis of VK2/E6E7 cells were analyzed using microscopy, Hoechst 33342/propidium iodide staining, lactate dehydrogenase release assay, gene and protein expression, co-immunoprecipitation, immunofluorescence, and enzyme-linked immunosorbent assay. (jcimjournal.com)

Subsequent mechanistic studies found that TGFβ1-induced enhancement of osteogenesis in BMP9-overexpressing C3H10T1/2 cells was accompanied by augmented expression of heat shock protein 47 (HSP47), a collagen-specific molecular chaperone essential for collagen biosynthesis, and can be attenuated by pirfenidone, a known anti-fibrotic inhibitor. (medsci.org)
Translational analysis of mouse and human placental protein and mRNA reveals distinct molecular pathologies in human preeclampsia. (udca.edu.co)

As the organizers of "nodes" in the intracellular signaling network, scaffold proteins may be of interest as potential therapeutic targets [ 2 ]. (biomedcentral.com)

AbbreviationsNoxNADPH oxidaseNRCMsneonatal rat cardiomyocytesCSMcigarette sidestream smoke cigarettes\formulated with mediumPLAproximity ligation assayBr\cAMP8\bromoadenosine 3,5\cyclic monophosphateMeHgmethyl mercuryTop2DNA topoisomerase IIMuRFmuscle band\finger proteins. (enmd-2076.com)

the kinase or catalytic domain and the PH domain. (wikipedia.org)

Moreover, our results provide further impetus for exploring the helix αC patches of other protein kinases as potential therapeutic targets even though they involve protein-protein interfaces. (rcsb.org)

CIP4 is a modular scaffold protein involved in the regulation of cellular morphology that can serve as an effector for the Rho family small GTPases Cdc42, TC10, and TCL [ 3 ]. (biomedcentral.com)

Active Akt inactivates Glycogen Synthase Kinase 3 (GSK3), eventually leading to the dephosphorylation and activation of glycogen synthase, and the stimulation of glycogen synthesis. (thermofisher.com)

The induction of reactive oxygen species by heme was dependent of Gα inhibitory protein and phosphoinositide 3-kinase and partially dependent of phospholipase Cβ, protein kinase C, mitogen-activated protein kinases, and Rho kinase. (neuroprobe.com)

The Son of Sevenless (Sos) proteins control receptor-mediated activation of Ras by catalyzing the exchange of guanosine diphosphate for guanosine triphosphate on Ras. (embl.de)

We show that Plasmodium berghei CDK-related kinase 5 (CRK5), is a critical regulator of atypical mitosis in the gametogony and is required for mosquito transmission. (elifesciences.org)
Our results provide evidence that during Plasmodium male gametogony, this divergent cyclin/CDK pair fills the functional space of other eukaryotic cell-cycle kinases controlling DNA replication. (elifesciences.org)

The anti-inflammatory actions of corticosteroids occur with a considerable delay (within hours or days) because of the multiple steps of cellular actions required to change protein expression. (ersjournals.com)
Methods: We treated non-small cell lung carcinoma cells (NSCLCs) with sub-therapeutic, therapeutic, and toxic concentrations of digitoxin and D6MA respectively, followed by both single point and real-time assays to evaluate changes in cellular gene and protein expression, adhesion, elasticity, and migration. (cdc.gov)

Cyclin-dependent kinases (CDKs) are key regulatory enzymes that control cell cycle transitions and the commitment to cell division. (nih.gov)
Cell cycle transitions are generally triggered by variation in the activity of cyclin-dependent kinases (CDKs) bound to cyclins. (elifesciences.org)
Central components of these networks are the cyclin-dependent kinases (CDKs). (elifesciences.org)
Of these, five are divergent CDK-related kinases (CRK), i.e. they are clearly related to CDKs but have no clear orthologues in the yeast or human kinomes. (elifesciences.org)

Reactivity with beta isoforms of p70 S6 Kinase is unknown. (rndsystems.com)

Progression through the cell cycle critically relies upon post-translational mechanisms including changes in activity of cell cycle kinases and phosphatases, and ubiquitin-mediated degradation of specific components once their function is complete. (elifesciences.org)
Further, it integrates many proteins to promote cancer progression. (medscape.com)
To evaluate the nature of cyclin-dependent kinase 5 (CDK5) hyperactivity in pancreatic cancer progression. (nih.gov)

CDK7 plays essential roles in both the cell cycle as a CDK-Activating Kinase (CAK) and in transcription as a component of the general transcription factor TFIIH. (umbc.edu)

Protein expression analysis, gene copy number analysis, and gene sequencing have yielded promising therapeutic targets for TNBC (Figure 1). (medscape.com)

Fibroblast growth factor 21 (FGF21), a secretion protein, functions as a pivotal regulator of energy metabolism and is being considered as a therapeutic candidate in metabolic syndromes. (hindawi.com)

Anatomy22

Organisms11

Chemicals and Drugs160

Analytical, Diagnostic and Therapeutic Techniques and Equipment14

Phenomena and Processes45

Information Science3

PDK113

PI3K11

Mitogen-activa4

Inhibitors4

Phosphorylation5

Serine5

Phosphatidylinositol5

Inhibition7

Pathways2

Signal transduction1

Pathway1

Inhibits2

Receptor tyrosi1

PDPK18

Downstream kinases1

Phosphorylates2

Activates1

Pleckstrin homology1

Pancreatic cancer cell1

Amplified and overexpressed1

Genes5

Calcium1

Receptors3

Membrane3

Enzyme2

Molecular2

Intracellular1

Cyclic1

Catalytic domain1

Potential therapeutic targets1

Scaffold1

Glycogen1

Phospholipase1

Activation1

Plasmodium2

Cellular2

CDKs4

Isoforms1

Progression3

Transcription1

Targets1

Regulator1