Target Information
Target General Infomation | |||||
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Target ID |
T20891
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Former ID |
TTDR00273
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Target Name |
3-phosphoinositide dependent protein kinase-1
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Gene Name |
PDPK1
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Synonyms |
3'-phosphoinositide dependent kinase 1; 3-Phosphoinositide-dependent kinase-1; HPDK1; PDPK1
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Target Type |
Clinical Trial
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Disease | Cancer [ICD9: 140-229; ICD10: C00-C96] | ||||
Lymphoma [ICD9: 202.8, 208.9; ICD10: C81-C86] | |||||
Function |
Serine/threonine kinase which acts as a master kinase, phosphorylating and activating a subgroup of the AGC family of protein kinases. Its targets include: protein kinase B (PKB/AKT1, PKB/AKT2, PKB/AKT3), p70 ribosomal protein S6 kinase (RPS6KB1), p90 ribosomal protein S6 kinase (RPS6KA1, RPS6KA2 and RPS6KA3), cyclic AMP-dependent protein kinase (PRKACA), protein kinase C (PRKCD and PRKCZ), serum and glucocorticoid-inducible kinase (SGK1, SGK2 and SGK3), p21-activated kinase-1 (PAK1), protein kinase PKN (PKN1 and PKN2). Plays a central role in the transduction of signals from insulin by providing the activating phosphorylation to PKB/AKT1, thus propagating the signal to downstream targets controlling cell proliferation and survival, as well as glucose and amino acid uptake and storage. Negatively regulates the TGF-beta-induced signaling by: modulating the association of SMAD3 and SMAD7 with TGF-beta receptor, phosphorylating SMAD2, SMAD3, SMAD4 and SMAD7, preventing the nuclear translocation of SMAD3 and SMAD4 and the translocation of SMAD7 from the nucleus to the cytoplasm in response to TGF-beta. Activates PPARG transcriptional activity and promotes adipocyte differentiation. Activates the NF-kappa-B pathway via phosphorylation of IKKB. The tyrosine phosphorylated form is crucial for the regulation of focal adhesions by angiotensin II. Controls proliferation, survival, and growth of developing pancreatic cells. Participates in the regulation of Ca(2+) entry and Ca(2+)-activated K(+) channels of mast cells. Essential for the motility of vascular endothelial cells (ECs) and is involved in the regulation of their chemotaxis. Plays a critical role in cardiac homeostasis by serving as a dual effector for cell survival and beta-adrenergic response. Plays an important role during thymocyte development by regulating the expression of key nutrient receptors on the surface of pre-T cells and mediating Notch-induced cell growth and proliferative responses. Provides negative feedback inhibition to toll-like receptor-mediated NF- kappa-B activation in macrophages. Isoform 3 is catalytically inactive.
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BioChemical Class |
Kinase
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UniProt ID | |||||
EC Number |
EC 2.7.11.1
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Sequence |
MARTTSQLYDAVPIQSSVVLCSCPSPSMVRTQTESSTPPGIPGGSRQGPAMDGTAAEPRP
GAGSLQHAQPPPQPRKKRPEDFKFGKILGEGSFSTVVLARELATSREYAIKILEKRHIIK ENKVPYVTRERDVMSRLDHPFFVKLYFTFQDDEKLYFGLSYAKNGELLKYIRKIGSFDET CTRFYTAEIVSALEYLHGKGIIHRDLKPENILLNEDMHIQITDFGTAKVLSPESKQARAN SFVGTAQYVSPELLTEKSACKSSDLWALGCIIYQLVAGLPPFRAGNEYLIFQKIIKLEYD FPEKFFPKARDLVEKLLVLDATKRLGCEEMEGYGPLKAHPFFESVTWENLHQQTPPKLTA YLPAMSEDDEDCYGNYDNLLSQFGCMQVSSSSSSHSLSASDTGLPQRSGSNIEQYIHDLD SNSFELDLQFSEDEKRLLLEKQAGGNPWHQFVENNLILKMGPVDKRKGLFARRRQLLLTE GPHLYYVDPVNKVLKGEIPWSQELRPEAKNFKTFFVHTPNRTYYLMDPSGNAHKWCRKIQ EVWRQRYQSHPDAAVQ |
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Drugs and Mode of Action | |||||
Pathways | |||||
KEGG Pathway | PPAR signaling pathway | ||||
FoxO signaling pathway | |||||
Sphingolipid signaling pathway | |||||
mTOR signaling pathway | |||||
PI3K-Akt signaling pathway | |||||
AMPK signaling pathway | |||||
Focal adhesion | |||||
T cell receptor signaling pathway | |||||
Fc epsilon RI signaling pathway | |||||
Neurotrophin signaling pathway | |||||
Insulin signaling pathway | |||||
Thyroid hormone signaling pathway | |||||
Aldosterone-regulated sodium reabsorption | |||||
Toxoplasmosis | |||||
Hepatitis C | |||||
Proteoglycans in cancer | |||||
Endometrial cancer | |||||
Prostate cancer | |||||
Non-small cell lung cancer | |||||
Choline metabolism in cancer | |||||
PANTHER Pathway | Inflammation mediated by chemokine and cytokine signaling pathway | ||||
Insulin/IGF pathway-protein kinase B signaling cascade | |||||
Interleukin signaling pathway | |||||
PDGF signaling pathway | |||||
PI3 kinase pathway | |||||
p53 pathway | |||||
Ras Pathway | |||||
p53 pathway feedback loops 2 | |||||
CCKR signaling map ST | |||||
Pathway Interaction Database | BCR signaling pathway | ||||
Insulin Pathway | |||||
TCR signaling in na& | |||||
#xef | |||||
ve CD4+ T cells | |||||
Signaling events mediated by Hepatocyte Growth Factor Receptor (c-Met) | |||||
TCR signaling in na& | |||||
ve CD8+ T cells | |||||
FAS (CD95) signaling pathway | |||||
mTOR signaling pathway | |||||
CXCR4-mediated signaling events | |||||
IGF1 pathway | |||||
Class I PI3K signaling events | |||||
ErbB1 downstream signaling | |||||
IL8- and CXCR2-mediated signaling events | |||||
CXCR3-mediated signaling events | |||||
VEGFR1 specific signals | |||||
Signaling events mediated by Stem cell factor receptor (c-Kit) | |||||
Signaling events mediated by VEGFR1 and VEGFR2 | |||||
Class I PI3K signaling events mediated by Akt | |||||
IL8- and CXCR1-mediated signaling events | |||||
Trk receptor signaling mediated by PI3K and PLC-gamma | |||||
FGF signaling pathway | |||||
TGF-beta receptor signaling | |||||
PathWhiz Pathway | Intracellular Signalling Through Adenosine Receptor A2a and Adenosine | ||||
Intracellular Signalling Through Adenosine Receptor A2b and Adenosine | |||||
Insulin Signalling | |||||
Reactome | GPVI-mediated activation cascade | ||||
PIP3 activates AKT signaling | |||||
Activation of AKT2 | |||||
Role of LAT2/NTAL/LAB on calcium mobilization | |||||
FCERI mediated NF-kB activation | |||||
Integrin alphaIIb beta3 signaling | |||||
CD28 dependent PI3K/Akt signaling | |||||
CTLA4 inhibitory signaling | |||||
gamma signalling through PI3Kgamma | |||||
VEGFR2 mediated vascular permeability | |||||
VEGFR2 mediated cell proliferation | |||||
CLEC7A (Dectin-1) signaling | |||||
RHO GTPases activate PKNs | |||||
Constitutive Signaling by AKT1 E17K in Cancer | |||||
WikiPathways | Serotonin HTR1 Group and FOS Pathway | ||||
TCR Signaling Pathway | |||||
Insulin Signaling | |||||
EGF/EGFR Signaling Pathway | |||||
Focal Adhesion | |||||
Cardiac Hypertrophic Response | |||||
Fc epsilon receptor (FCERI) signaling | |||||
Neurotransmitter Receptor Binding And Downstream Transmission In The Postsynaptic Cell | |||||
Signaling by Type 1 Insulin-like Growth Factor 1 Receptor (IGF1R) | |||||
PIP3 activates AKT signaling | |||||
BDNF signaling pathway | |||||
Interleukin-11 Signaling Pathway | |||||
B Cell Receptor Signaling Pathway | |||||
Signaling Pathways in Glioblastoma | |||||
TSH signaling pathway | |||||
TCR signaling | |||||
Signaling by Insulin receptor | |||||
Integrin-mediated Cell Adhesion | |||||
GPVI-mediated activation cascade | |||||
GPCR downstream signaling | |||||
Costimulation by the CD28 family | |||||
MicroRNAs in cardiomyocyte hypertrophy | |||||
References | |||||
Ref 525397 | Genetic inactivation or pharmacological inhibition of Pdk1 delays development and inhibits metastasis of Braf(V600E)::Pten(-/-) melanoma. Oncogene. 2014 Aug 21;33(34):4330-9. | ||||
Ref 527484 | Novel small molecule inhibitors of 3-phosphoinositide-dependent kinase-1. J Biol Chem. 2005 May 20;280(20):19867-74. Epub 2005 Mar 16. | ||||
Ref 530572 | 2,3,5-Trisubstituted pyridines as selective AKT inhibitors. Part II: Improved drug-like properties and kinase selectivity from azaindazoles. Bioorg Med Chem Lett. 2010 Jan 15;20(2):679-83. | ||||
Ref 530764 | Molecular pharmacology and antitumor activity of PHT-427, a novel Akt/phosphatidylinositide-dependent protein kinase 1 pleckstrin homology domain inhibitor. Mol Cancer Ther. 2010 Mar;9(3):706-17. |
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