General Information of the Molecule (ID: Mol00135)
Name
phosphoinositide-3-dependent protein kinase 1 (PDPK1) ,Homo sapiens
Synonyms
hPDK1; PDK1
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Molecule Type
Protein
Gene Name
PDPK1
Gene ID
5170
Location
chr16:2537979-2603188[+]
Sequence
MARTTSQLYDAVPIQSSVVLCSCPSPSMVRTQTESSTPPGIPGGSRQGPAMDGTAAEPRP
GAGSLQHAQPPPQPRKKRPEDFKFGKILGEGSFSTVVLARELATSREYAIKILEKRHIIK
ENKVPYVTRERDVMSRLDHPFFVKLYFTFQDDEKLYFGLSYAKNGELLKYIRKIGSFDET
CTRFYTAEIVSALEYLHGKGIIHRDLKPENILLNEDMHIQITDFGTAKVLSPESKQARAN
SFVGTAQYVSPELLTEKSACKSSDLWALGCIIYQLVAGLPPFRAGNEYLIFQKIIKLEYD
FPEKFFPKARDLVEKLLVLDATKRLGCEEMEGYGPLKAHPFFESVTWENLHQQTPPKLTA
YLPAMSEDDEDCYGNYDNLLSQFGCMQVSSSSSSHSLSASDTGLPQRSGSNIEQYIHDLD
SNSFELDLQFSEDEKRLLLEKQAGGNPWHQFVENNLILKMGPVDKRKGLFARRRQLLLTE
GPHLYYVDPVNKVLKGEIPWSQELRPEAKNFKTFFVHTPNRTYYLMDPSGNAHKWCRKIQ
EVWRQRYQSHPDAAVQ
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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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Uniprot ID
PDPK1_HUMAN
Ensembl ID
ENSG00000140992
HGNC ID
HGNC:8816
        Click to Show/Hide the Complete Species Lineage
Kingdom: Metazoa
Phylum: Chordata
Class: Mammalia
Order: Primates
Family: Hominidae
Genus: Homo
Species: Homo sapiens
Type(s) of Resistant Mechanism of This Molecule
  UAPP: Unusual Activation of Pro-survival Pathway
Drug Resistance Data Categorized by Drug
Approved Drug(s)
4 drug(s) in total
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Erlotinib
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Drug Resistance Data Categorized by Their Corresponding Mechanisms
       Unusual Activation of Pro-survival Pathway (UAPP) Click to Show/Hide
Disease Class: Non-small cell lung cancer [1]
Resistant Disease Non-small cell lung cancer [ICD-11: 2C25.Y]
Resistant Drug Erlotinib
Molecule Alteration Expression
Up-regulation
Experimental Note Identified from the Human Clinical Data
Cell Pathway Regulation Cell invasion Activation hsa05200
Cell proliferation Activation hsa05200
miR1183/PDPk1 signaling pathway Activation hsa05206
In Vitro Model H1975 cells Lung Homo sapiens (Human) CVCL_1511
A549 cells Lung Homo sapiens (Human) CVCL_0023
H1299 cells Lung Homo sapiens (Human) CVCL_0060
HCC827 cells Lung Homo sapiens (Human) CVCL_2063
NCI-H358 cells Lung Homo sapiens (Human) CVCL_1559
Experiment for
Molecule Alteration
Western blot analysis; RT-qPCR; Luciferase reporter assay
Experiment for
Drug Resistance
MTT assay; Colony formation assay
Mechanism Description Hsa_circ_0004015 formed by CDk14 gene inhibited the expression of miR-1183, which could disinhibit the PDPk1 expression from miR-1183, ultimately resulted in the promotion of cell proliferation, invasion, and TkI inhibitor drug resistance of NSCLC cells.
Gefitinib
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Drug Resistance Data Categorized by Their Corresponding Mechanisms
       Unusual Activation of Pro-survival Pathway (UAPP) Click to Show/Hide
Disease Class: Non-small cell lung cancer [1]
Resistant Disease Non-small cell lung cancer [ICD-11: 2C25.Y]
Resistant Drug Gefitinib
Molecule Alteration Expression
Up-regulation
Experimental Note Identified from the Human Clinical Data
Cell Pathway Regulation Cell invasion Activation hsa05200
Cell proliferation Activation hsa05200
miR1183/PDPk1 signaling pathway Activation hsa05206
In Vitro Model H1975 cells Lung Homo sapiens (Human) CVCL_1511
A549 cells Lung Homo sapiens (Human) CVCL_0023
H1299 cells Lung Homo sapiens (Human) CVCL_0060
HCC827 cells Lung Homo sapiens (Human) CVCL_2063
NCI-H358 cells Lung Homo sapiens (Human) CVCL_1559
Experiment for
Molecule Alteration
Western blot analysis; RT-qPCR; Luciferase reporter assay
Experiment for
Drug Resistance
MTT assay; Colony formation assay
Mechanism Description Hsa_circ_0004015 formed by CDk14 gene inhibited the expression of miR-1183, which could disinhibit the PDPk1 expression from miR-1183, ultimately resulted in the promotion of cell proliferation, invasion, and TkI inhibitor drug resistance of NSCLC cells.
Icotinib hydrochloride
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Drug Resistance Data Categorized by Their Corresponding Mechanisms
       Unusual Activation of Pro-survival Pathway (UAPP) Click to Show/Hide
Disease Class: Non-small cell lung cancer [1]
Resistant Disease Non-small cell lung cancer [ICD-11: 2C25.Y]
Resistant Drug Icotinib hydrochloride
Molecule Alteration Expression
Up-regulation
Experimental Note Identified from the Human Clinical Data
Cell Pathway Regulation Cell invasion Activation hsa05200
Cell proliferation Activation hsa05200
miR1183/PDPk1 signaling pathway Activation hsa05206
In Vitro Model H1975 cells Lung Homo sapiens (Human) CVCL_1511
A549 cells Lung Homo sapiens (Human) CVCL_0023
H1299 cells Lung Homo sapiens (Human) CVCL_0060
HCC827 cells Lung Homo sapiens (Human) CVCL_2063
NCI-H358 cells Lung Homo sapiens (Human) CVCL_1559
Experiment for
Molecule Alteration
Western blot analysis; RT-qPCR; Luciferase reporter assay
Experiment for
Drug Resistance
MTT assay; Colony formation assay
Mechanism Description Hsa_circ_0004015 formed by CDk14 gene inhibited the expression of miR-1183, which could disinhibit the PDPk1 expression from miR-1183, ultimately resulted in the promotion of cell proliferation, invasion, and TkI inhibitor drug resistance of NSCLC cells.
Dichloroacetate
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Drug Resistance Data Categorized by Their Corresponding Mechanisms
       Unusual Activation of Pro-survival Pathway (UAPP) Click to Show/Hide
Disease Class: Glioblastoma [2]
Resistant Disease Glioblastoma [ICD-11: 2A00.02]
Resistant Drug Dichloroacetate
Molecule Alteration Expression
Up-regulation
Experimental Note Identified from the Human Clinical Data
Cell Pathway Regulation Cell migration Activation hsa04670
Cell proliferation Activation hsa05200
In Vitro Model DBTRG cells Brain Homo sapiens (Human) CVCL_1169
Experiment for
Molecule Alteration
Western blot analysis; RT-qPCR
Experiment for
Drug Resistance
Colorimetric SRB assay
Mechanism Description The potential of miR-144 overexpression to reduce GB cell malignancy, both by decreasing Cell migration and invasion abilities and by sensitizing resistant tumor cells to chemotherapy, paving the way to a novel and more effective GB therapy.
Investigative Drug(s)
1 drug(s) in total
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PI3K pathway inhibitors
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Drug Sensitivity Data Categorized by Their Corresponding Mechanisms
       Unusual Activation of Pro-survival Pathway (UAPP) Click to Show/Hide
Disease Class: Breast adenocarcinoma [3]
Sensitive Disease Breast adenocarcinoma [ICD-11: 2C60.1]
Sensitive Drug PI3K pathway inhibitors
Molecule Alteration Copy number gain
.
Experimental Note Identified from the Human Clinical Data
In Vitro Model Breast .
In Vivo Model SCID/NCr (BALB/c background) mouse xenograft model Mus musculus
Experiment for
Molecule Alteration
Immunoblotting analysis
Mechanism Description The copy number gain in gene PDPK1 cause the sensitivity of PI3K pathway inhibitors by unusual activation of pro-survival pathway.
Disease- and Tissue-specific Abundances of This Molecule
ICD Disease Classification 02
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Brain cancer [ICD-11: 2A00]
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Differential expression of molecule in resistant diseases
The Studied Tissue Nervous tissue
The Specified Disease Brain cancer
The Expression Level of Disease Section Compare with the Healthy Individual Tissue p-value: 1.27E-130; Fold-change: -5.10E-01; Z-score: -1.73E+00
Molecule expression in the diseased tissue of patients
Molecule expression in the normal tissue of healthy individuals
Disease-specific Molecule Abundances Click to View the Clearer Original Diagram
The Studied Tissue Brainstem tissue
The Specified Disease Glioma
The Expression Level of Disease Section Compare with the Healthy Individual Tissue p-value: 4.26E-02; Fold-change: -2.56E-01; Z-score: -3.17E+00
Molecule expression in the diseased tissue of patients
Molecule expression in the normal tissue of healthy individuals
Disease-specific Molecule Abundances Click to View the Clearer Original Diagram
The Studied Tissue White matter
The Specified Disease Glioma
The Expression Level of Disease Section Compare with the Healthy Individual Tissue p-value: 1.77E-01; Fold-change: 1.36E-01; Z-score: 7.98E-01
Molecule expression in the diseased tissue of patients
Molecule expression in the normal tissue of healthy individuals
Disease-specific Molecule Abundances Click to View the Clearer Original Diagram
The Studied Tissue Brainstem tissue
The Specified Disease Neuroectodermal tumor
The Expression Level of Disease Section Compare with the Healthy Individual Tissue p-value: 2.99E-03; Fold-change: 2.98E-01; Z-score: 9.97E-01
Molecule expression in the diseased tissue of patients
Molecule expression in the normal tissue of healthy individuals
Disease-specific Molecule Abundances Click to View the Clearer Original Diagram
Lung cancer [ICD-11: 2C25]
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Differential expression of molecule in resistant diseases
The Studied Tissue Lung
The Specified Disease Lung cancer
The Expression Level of Disease Section Compare with the Healthy Individual Tissue p-value: 8.73E-09; Fold-change: 2.51E-01; Z-score: 8.32E-01
The Expression Level of Disease Section Compare with the Adjacent Tissue p-value: 7.21E-06; Fold-change: 1.84E-01; Z-score: 3.88E-01
Molecule expression in the normal tissue adjacent to the diseased tissue of patients
Molecule expression in the diseased tissue of patients
Molecule expression in the normal tissue of healthy individuals
Disease-specific Molecule Abundances Click to View the Clearer Original Diagram
Breast cancer [ICD-11: 2C60]
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Differential expression of molecule in resistant diseases
The Studied Tissue Breast tissue
The Specified Disease Breast cancer
The Expression Level of Disease Section Compare with the Healthy Individual Tissue p-value: 3.41E-01; Fold-change: 2.00E-02; Z-score: 6.33E-02
The Expression Level of Disease Section Compare with the Adjacent Tissue p-value: 1.13E-05; Fold-change: 5.85E-01; Z-score: 1.14E+00
Molecule expression in the normal tissue adjacent to the diseased tissue of patients
Molecule expression in the diseased tissue of patients
Molecule expression in the normal tissue of healthy individuals
Disease-specific Molecule Abundances Click to View the Clearer Original Diagram
Tissue-specific Molecule Abundances in Healthy Individuals
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References
Ref 1 Circular RNA hsa_circ_0004015 regulates the proliferation, invasion, and TKI drug resistance of non-small cell lung cancer by miR-1183/PDPK1 signaling pathway. Biochem Biophys Res Commun. 2019 Jan 8;508(2):527-535. doi: 10.1016/j.bbrc.2018.11.157. Epub 2018 Nov 30.
Ref 2 MiR-144 overexpression as a promising therapeutic strategy to overcome glioblastoma cell invasiveness and resistance to chemotherapy. Hum Mol Genet. 2019 Aug 15;28(16):2738-2751. doi: 10.1093/hmg/ddz099.
Ref 3 3-Phosphoinositide-dependent kinase 1 potentiates upstream lesions on the phosphatidylinositol 3-kinase pathway in breast carcinomaCancer Res. 2009 Aug 1;69(15):6299-306. doi: 10.1158/0008-5472.CAN-09-0820. Epub 2009 Jul 14.

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