Target General Infomation
Target ID
T08074
Former ID
TTDR01345
Target Name
mRNA of PDK-1
Gene Name
PDPK1
Synonyms
3phosphoinositidedependent protein kinase 1 (mRNA) (mRNA); PDPK1 (mRNA) (mRNA); hPDK1 (mRNA) (mRNA); PDPK1
Target Type
Research
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.
BioChemical Class
Kinase
Target Validation
T08074
UniProt ID
EC Number
EC 2.7.11.1
Sequence
MARTTSQLYDAVPIQSSVVLCSCPSPSMVRTQTESSTPPGIPGGSRQGPAMDGTAAEPRP
GAGSLQHAQPPPQPRKKRPEDFKFGKILGEGSFSTVVLARELATSREYAIKILEKRHIIK
ENKVPYVTRERDVMSRLDHPFFVKLYFTFQDDEKLYFGLSYAKNGELLKYIRKIGSFDET
CTRFYTAEIVSALEYLHGKGIIHRDLKPENILLNEDMHIQITDFGTAKVLSPESKQARAN
SFVGTAQYVSPELLTEKSACKSSDLWALGCIIYQLVAGLPPFRAGNEYLIFQKIIKLEYD
FPEKFFPKARDLVEKLLVLDATKRLGCEEMEGYGPLKAHPFFESVTWENLHQQTPPKLTA
YLPAMSEDDEDCYGNYDNLLSQFGCMQVSSSSSSHSLSASDTGLPQRSGSNIEQYIHDLD
SNSFELDLQFSEDEKRLLLEKQAGGNPWHQFVENNLILKMGPVDKRKGLFARRRQLLLTE
GPHLYYVDPVNKVLKGEIPWSQELRPEAKNFKTFFVHTPNRTYYLMDPSGNAHKWCRKIQ
EVWRQRYQSHPDAAVQ
Structure
1H1W; 1OKY; 1OKZ; 1UU3; 1UU7; 1UU8; 1UU9; 1UVR; 1W1D; 1W1G; 1W1H; 1Z5M; 2BIY; 2PE0; 2PE1; 2PE2; 2R7B; 2VKI; 2XCH; 2XCK; 3H9O; 3HRC; 3HRF; 3ION; 3IOP; 3NAX; 3NAY; 3NUN; 3NUS; 3NUU; 3NUY; 3ORX; 3ORZ; 3OTU; 3PWY; 3QC4; 3QCQ; 3QCS; 3QCX; 3QCY; 3QD0; 3QD3; 3QD4; 3RCJ; 3RWP; 3RWQ; 3SC1; 4A06; 4A07; 4AW0; 4AW1; 4CT1; 4CT2; 4RQK; 4RQV; 4RRV
Inhibitor (Z)-3-((1H-pyrrol-2-yl)methylene)indolin-2-one Drug Info [528864]
BX-201 Drug Info [528864]
BX-517 Drug Info [528864]
NU-6102 Drug Info [527906]
SU-6689 Drug Info [528864]
Binder MiR-375 Drug Info [536758]
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&amp
#xef
ve CD4+ T cells
Signaling events mediated by Hepatocyte Growth Factor Receptor (c-Met)
TCR signaling in na&amp
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
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 527906Bioorg Med Chem Lett. 2006 Mar 1;16(5):1353-7. Epub 2005 Dec 1.Triazolo[1,5-a]pyrimidines as novel CDK2 inhibitors: protein structure-guided design and SAR.
Ref 528864Bioorg Med Chem Lett. 2007 Jul 15;17(14):3814-8. Epub 2007 Apr 27.Indolinone based phosphoinositide-dependent kinase-1 (PDK1) inhibitors. Part 1: design, synthesis and biological activity.
Ref 536758miR-375 targets 3'-phosphoinositide-dependent protein kinase-1 and regulates glucose-induced biological responses in pancreatic beta-cells. Diabetes. 2008 Oct;57(10):2708-17. Epub 2008 Jun 30.
Ref 549612US patent application no. 6,124,272, Antisense modulation of PDK-1 expression.

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