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AKT1 — ILK
Pathways - manually collected, often from reviews:
-
OpenBEL Selventa BEL large corpus:
AKT1
→
ILK
(directlyIncreases, AKT1 Activity)
Evidence: 11313365;10226025
-
BioCarta pten dependent cell cycle arrest and apoptosis:
ILK
→
AKT (AKT1)
(modification, activates)
-
KEGG Focal adhesion:
ILK
→
AKT1/AKT2/AKT3
(protein-protein, phosphorylation)
-
KEGG Endometrial cancer:
ILK
→
AKT1/AKT2/AKT3
(protein-protein, activation)
-
NCI Pathway Database Integrins in angiogenesis:
ILK (ILK)
→
AKT1 (AKT1)
(modification, activates)
Persad et al., J Biol Chem 2001
-
NCI Pathway Database Integrin-linked kinase signaling:
ILK/RICTOR complex (ILK-RICTOR)
→
AKT1 (AKT1)
(modification, activates)
McDonald et al., Cancer Res 2008*
Evidence: assay, physical interaction
-
NCI Pathway Database Integrin-linked kinase signaling:
ILK/PINCH1/alpha parvin complex (ILK-LIMS1-PARVA)
→
AKT1 (AKT1)
(modification, inhibits)
Wu et al., J Cell Sci 1999*, Attwell et al., Oncogene 2000*, Persad et al., J Biol Chem 2001, Fukuda et al., J Biol Chem 2003, Qian et al., Oncogene 2005*, Wilson et al., Biochem J 2005*, Joshi et al., FASEB J 2007*, Delcommenne et al., Proc Natl Acad Sci U S A 1998
Evidence: mutant phenotype, assay
-
WikiPathways Focal Adhesion:
ILK
→
AKT1/AKT2/AKT3
(activation)
Protein-Protein interactions - manually collected from original source literature:
Studies that report less than 10 interactions are marked with *
-
IRef Biogrid Interaction:
AKT1
—
ILK
(physical association, affinity chromatography technology)
Barry et al., J Biol Chem 2002*
-
IRef Biogrid Interaction:
AKT1
—
ILK
(direct interaction, enzymatic study)
Delcommenne et al., Proc Natl Acad Sci U S A 1998
-
IRef Biogrid Interaction:
AKT1
—
ILK
(physical association, affinity chromatography technology)
Persad et al., J Biol Chem 2001
-
IRef Hprd Interaction:
AKT1
—
ILK
(in vivo)
Matsumoto et al., J Biol Chem 2001*, Chen et al., J Biol Chem 2001*, Hellyer et al., J Biol Chem 2001*, Conus et al., J Biol Chem 2002*, Hill et al., Curr Biol 2002*, Shenoy et al., J Immunol 2003*, Delcommenne et al., Proc Natl Acad Sci U S A 1998
-
IRef Hprd Interaction:
AKT1
—
ILK
(in vitro)
Matsumoto et al., J Biol Chem 2001*, Chen et al., J Biol Chem 2001*, Hellyer et al., J Biol Chem 2001*, Conus et al., J Biol Chem 2002*, Hill et al., Curr Biol 2002*, Shenoy et al., J Immunol 2003*, Delcommenne et al., Proc Natl Acad Sci U S A 1998
-
IRef Ophid Interaction:
AKT1
—
ILK
(aggregation, interologs mapping)
Brown et al., Bioinformatics 2005
Text-mined interactions from Literome
Troussard et al., Mol Cell Biol 1999
:
ILK activates
protein kinase B and inhibits the glycogen synthase kinase 3 ( GSK-3 ) activity in a phosphatidylinositol-3-kinase ( PI 3-kinase ) -dependent manner
Lynch et al., Oncogene 1999
:
Mutation of this serine to aspartate or glutamate, but not alanine, in combination with the inactivating lysine mutation restores
integrin linked kinase dependent phosphorylation of serine-473 of
protein kinase B
Persad et al., Proc Natl Acad Sci U S A 2000
(Prostatic Neoplasms) :
Transfection of dominant negative
ILK and WT PTEN into these cells also
results in the inhibition of
PKB/Akt kinase activity ... Transfection of dominant negative
ILK and WT PTEN into these cells also
results in the inhibition of
PKB/Akt kinase activity
D'Amico et al., J Biol Chem 2000
(Breast Neoplasms) :
Inhibition of the PI 3-kinase and
AKT/protein kinase B , but not of the p38, ERK, or JNK signaling pathways,
reduced ILK induction of cyclin D1 expression ... Inhibition of the PI 3-kinase and
AKT/protein kinase B, but not of the p38, ERK, or JNK signaling pathways,
reduced ILK induction of cyclin D1 expression
Yoganathan et al., Biochem Pharmacol 2000
:
A small molecule
ILK inhibitor
suppresses the phosphorylation of
PKB at the Ser-473 but not the Thr-308 site in the PTEN mutant cells
Persad et al., J Biol Chem 2001
:
Regulation of
protein kinase B/Akt-serine 473 phosphorylation by
integrin linked kinase : critical roles for kinase activity and amino acids arginine 211 and serine 343 ...
Regulation of protein kinase
B/Akt-serine 473 phosphorylation by
integrin linked kinase : critical roles for kinase activity and amino acids arginine 211 and serine 343 ... A highly selective small molecule inhibitor of
ILK activity also
inhibits the ability of ILK to phosphorylate
PKB/Akt in vitro and in intact cells ... A highly selective small molecule inhibitor of
ILK activity also
inhibits the ability of ILK to phosphorylate
PKB/Akt in vitro and in intact cells
Tan et al., J Biol Chem 2002
:
Overexpression of
ILK stimulated NF-kappaB activity and inhibition of ILK or
protein kinase B ( PKB/Akt ) suppressed this activation
Gary et al., J Neurochem 2003
:
Instead, we show a
requirement for
ILK in integrin receptor induced
Akt activation ... ILK was activated following integrin stimulation and dominant negative
ILK blocked integrin mediated
Akt activation and cell survival
Cruet-Hennequart et al., Oncogene 2003
(Adenocarcinoma...) :
Inhibition of
ILK by a pharmacological inhibitor
results in inhibition of cell proliferation,
PKB/Akt phosphorylation and increase of p27 ( Kip1 ) ... Inhibition of
ILK by a pharmacological inhibitor
results in inhibition of cell proliferation,
PKB/Akt phosphorylation and increase of p27 ( Kip1 )
Troussard et al., J Biol Chem 2003
:
Utilizing double stranded RNA interference ( siRNA ) as well as conditional knock-out of ILK using the Cre-Lox system, we now demonstrate that
ILK is
essential for the regulation of
PKB/Akt activity ... Utilizing double stranded RNA interference ( siRNA ) as well as conditional knock-out of ILK using the Cre-Lox system, we now demonstrate that
ILK is
essential for the regulation of
PKB/Akt activity
Persad et al., Cancer Metastasis Rev 2003
(Cell Transformation, Neoplastic...) :
ILK can
mediate the phosphorylation of a variety of intracellular substrates, most notable of which are :
protein kinase B ( PKB/Akt ), glycogen synthase kinase-3 ( GSK-3 ) and myosin light chain
Fukuda et al., J Biol Chem 2003
:
Third, PINCH-1 and
ILK are
required for optimal activating phosphorylation of
PKB/Akt , an important signaling intermediate of the survival pathway ... Third, PINCH-1 and
ILK are
required for optimal activating phosphorylation of
PKB/Akt , an important signaling intermediate of the survival pathway ... Whereas depletion of
ILK reduced Ser473 phosphorylation but not Thr308 phosphorylation of
PKB/Akt , depletion of PINCH-1 reduced both the Ser473 and Thr308 phosphorylation of PKB/Akt ... Whereas depletion of
ILK reduced Ser473 phosphorylation but not Thr308 phosphorylation of
PKB/Akt , depletion of PINCH-1 reduced both the Ser473 and Thr308 phosphorylation of PKB/Akt
Kaneko et al., J Cell Sci 2004
:
VEGF induced phosphorylation of
protein kinase B ( PKB/Akt ), a regulator of cell survival and apoptosis, on serine 473, but not on threonine 308, in an
ILK dependent manner
Makino et al., Oncogene 2004
:
Stable expression of
ILK-KD in HER2/neu transformed cells
suppressed Akt phosphorylation and the expression of IkappaB kinase alpha and beta ( IKKalpha and beta ) at both the protein and mRNA levels, preventing IkappaB-alpha degradation and NF-kappaB activation
Lee et al., Biochem Biophys Res Commun 2004
:
TGFbeta mediated phosphorylation of
Akt at Ser-473 was
inhibited by dominant negative
ILK and PI3K inhibitors, LY294002 and wortmannin
Yau et al., Cancer Res 2005
(Neovascularization, Pathologic...) :
Inhibition of
integrin linked kinase by a selective small molecule inhibitor, QLT0254,
inhibits the
PI3K/PKB/mTOR , Stat3, and FKHR pathways and tumor growth, and enhances gemcitabine induced apoptosis in human orthotopic primary pancreatic cancer xenografts ... These results show in vivo evidence that
ILK plays a prominent role in oncogenic phosphatidylinositol
3-kinase/PKB signaling in vivo with major impact on the mammalian target of rapamycin, signal transducers and activators of transcription 3, and forkhead in rhadomyosarcoma signaling pathways, suggesting that ILK inhibitors might show activity in pancreatic cancer patients
Edwards et al., Oncogene 2005
(Brain Neoplasms...) :
Inhibition of
ILK in PTEN-mutant human glioblastomas
inhibits PKB/Akt activation, induces apoptosis, and delays tumor growth ... Inhibition of
ILK in PTEN-mutant human glioblastomas
inhibits PKB/Akt activation, induces apoptosis, and delays tumor growth ... We now demonstrate that
ILK activity
regulates PKB/Akt activity in glioblastoma cells ... We now demonstrate that
ILK activity
regulates PKB/Akt activity in glioblastoma cells
Nho et al., J Biol Chem 2005
:
Role of
integrin linked kinase in regulating phosphorylation of
Akt and fibroblast survival in type I collagen matrices through a beta1 integrin viability signaling pathway ... Kinase dead ILK attenuated Akt phosphorylation and enhanced fibroblast apoptosis, whereas hyperactive and wild type
ILK augmented
Akt phosphorylation and protected fibroblasts from apoptosis ... These data establish that matrix derived mechanical forces sensed by beta1 integrin are capable of modulating
ILK activity which regulates fibroblast viability via an
Akt dependent mechanism
Zhang et al., Hepatology 2006
(Disease Progression...) :
Our studies also showed that
ILK is
involved in the phosphorylation of ERK 1/2, p38 MAPK, JNK, and
PKB and that selective inhibition of ILK expression by siRNA results in a significant decrease in their phosphorylation
Shi et al., Oncogene 2007
(Brain Neoplasms...) :
Downregulation of either FAK or
ILK expression
inhibited SPARC mediated
AKT phosphorylation, and targeting both FAK and ILK attenuated AKT activation more potently than targeting either FAK or ILK alone
Joshi et al., FASEB J 2007
:
Integrin linked kinase (ILK) , a membrane proximal upstream
regulator of
Akt and GSK3beta, was considered a candidate signaling mediator for T-cad
Hehlgans et al., Radiother Oncol 2008
:
ILK regulated
AKT activity in a phosphatidylinositol-3 kinase (PI3K) dependent manner
Wang et al., J Cell Biol 2008
(Muscular Dystrophy, Animal) :
ILK binds the cytoplasmic domain of beta1 integrin and
mediates phosphorylation of
protein kinase B (PKB)/Akt , which in turn plays a central role during skeletal muscle regeneration ...
ILK binds the cytoplasmic domain of beta1 integrin and
mediates phosphorylation of protein kinase B
(PKB)/Akt , which in turn plays a central role during skeletal muscle regeneration
McDonald et al., Cancer Res 2008
(Breast Neoplasms...) :
Rictor and
integrin linked kinase interact and
regulate Akt phosphorylation and cancer cell survival
Hinton et al., J Cell Mol Med 2008
(Breast Neoplasms...) :
Upon stimulation by growth factors and chemokine ligands,
integrin linked kinase mediates the phosphorylation of
Akt Ser473, and glycogen synthase kinase-3
Fuchs et al., Cancer Res 2008
(Carcinoma, Hepatocellular...) :
Mesenchymal cell lines were therefore experimentally transformed with kinase-inactive ILK ( KI-ILK ) with a resulting decrease in
ILK activity and
activation of
AKT
Verreault et al., Oligonucleotides 2009
(Neoplasms) :
siRNA mediated
integrin linked kinase suppression : nonspecific effects of siRNA/cationic liposome complexes
trigger changes in the expression of
phosphorylated-AKT and mTOR independently of ILK silencing
Huang et al., Microcirculation 2010
(Mechanotransduction, Cellular) :
ILK was localized to FA and silencing
ILK promoted cell spreading, enhanced cell adhesion, reduced cell proliferation and
reduced downstream phosphorylation of GSK-3beta and
PKB/Akt ... ILK was localized to FA and silencing
ILK promoted cell spreading, enhanced cell adhesion, reduced cell proliferation and
reduced downstream phosphorylation of GSK-3beta and
PKB/Akt
Wu et al., Am J Nephrol 2010
:
LXA ( 4 ) inhibited the expression and activity of
ILK and
activation of Ras, ERK1/2, PI3-K and
Akt in HK-2 cells stimulated by CTGF
Kalra et al., Oncogene 2010
:
Time course studies suggest that
ILK inhibition or silencing
caused transient decreases in
P-AKT ( ser473 ), which were not temporally related to Her2/neu downregulation
Taylor et al., Surgery 2011
(Neuroblastoma) :
Integrin linked kinase (ILK) induces phosphorylation of
Akt leading to an increase in cell survival
Hwangbo et al., J Biol Chem 2011
:
Inhibition of mda-9/syntenin or expression of mutant
ILK ( E359K ) significantly
blocked the translocation of both ILK and
Akt to the plasma membrane
Delcommenne et al., Proc Natl Acad Sci U S A 1998
:
Phosphoinositide-3-OH kinase dependent
regulation of glycogen synthase kinase 3 and
protein kinase B/AKT by the
integrin linked kinase ... Phosphoinositide-3-OH kinase dependent
regulation of glycogen synthase kinase 3 and protein kinase
B/AKT by the
integrin linked kinase ... In addition, kinase-active ILK can phosphorylate PKB/AKT on serine-473, whereas kinase-deficient
ILK severely
inhibits endogenous phosphorylation of
PKB/AKT on serine-473, demonstrating that ILK is involved in agonist stimulated, Pi(3)K dependent, PKB/AKT activation ... In addition, kinase-active ILK can phosphorylate PKB/AKT on serine-473, whereas kinase-deficient
ILK severely
inhibits endogenous phosphorylation of
PKB/AKT on serine-473, demonstrating that ILK is involved in agonist stimulated, Pi(3)K dependent, PKB/AKT activation