◀ Back to AKT1
AKT1 — SRC
Pathways - manually collected, often from reviews:
-
OpenBEL Selventa BEL large corpus:
AKT1
→
SRC
(increases, SRC Activity, AKT1 Activity)
Tanno et al., Cancer Res 2001*
Evidence: The downstream targets of Src that lead to the up-regulation of IGF-IR expression were previously unknown. We demonstrate here that AKT regulates IGF-IR expression in PANC-1
-
OpenBEL Selventa BEL large corpus:
AKT1
→
SRC
(increases, SRC Activity, AKT1 Activity)
Morel et al., J Biol Chem 2002*
Evidence: Modified assertion
-
NCI Pathway Database Plasma membrane estrogen receptor signaling:
E2/ER alpha (dimer)/PELP1/Src/PI3K complex (ESR1-PELP1-SRC-PIK3CA-PIK3R1)
→
AKT1 (AKT1)
(modification, activates)
Haynes et al., Circ Res 2000, Hisamoto et al., J Biol Chem 2001, Haynes et al., J Biol Chem 2003, Greger et al., Mol Cell Biol 2007
Evidence: assay
Protein-Protein interactions - manually collected from original source literature:
Studies that report less than 10 interactions are marked with *
Text-mined interactions from Literome
Hakak et al., Oncogene 2000
:
Shp-2 mediates
v-Src induced morphological changes and
activation of the anti-apoptotic protein kinase
Akt ... Shp-2 deficiency also reduced
v-Src induced activation of the anti-apoptotic protein kinase
Akt
Sumitomo et al., Cancer Res 2001
(Prostatic Neoplasms) :
Incubation of TSU-Pr1 cells with specific kinase inhibitors together with ET-1 or bombesin showed that IGF-IR activation is required for neuropeptide induced Akt phosphorylation, and that neuropeptide induced
Akt activation is predominantly
mediated by
Src and phosphatidylinositol 3-kinase but not by mitogen activated protein kinase or protein kinase C
Endo et al., Exp Hematol 2001
:
These data indicate that SCF protects purified human GPA+c-kit+ cells from apoptosis and suggest that kit mediated
Src kinase activation is
involved in
Akt activation and cell survival
Castoria et al., EMBO J 2001
(Breast Neoplasms) :
The
Src inhibitor, PP1,
prevents hormone stimulation of
Akt and PI3-kinase activities in MCF-7 cells
Morel et al., J Biol Chem 2002
(Arthritis, Rheumatoid...) :
AS
c-Src ODN
inhibited Akt phosphorylation, confirming Src is upstream of PI3-kinase in IL-18 induced RA synovial fibroblast signaling
Schmitt et al., J Biol Chem 2002
(MAP Kinase Signaling System) :
Interestingly, beta-adrenergic stimulation of both Rap1 and ERKs, but not Ras and
AKT , can be
blocked by a
Src mutant ( SrcS17A ) that is incapable of being phosphorylated and activated by PKA ... Furthermore, a
Src mutant ( SrcS17D ), which mimics PKA phosphorylation at serine 17, stimulates Rap1 activation, Rap1/B-Raf association, and ERK activation but does not
stimulate Ras or
AKT
Haynes et al., J Biol Chem 2003
:
Moreover, transfection of kinase-dead
c-Src inhibited 17beta-estradiol induced
Akt phosphorylation, whereas constitutively active c-Src increased basal Akt phosphorylation
Hauck et al., EMBO J 2002
(Lung Neoplasms) :
However, FRNK did not affect
v-Src stimulated
Akt activation, cell growth in soft agar, or subcutaneous tumor formation in nude mice
Jiang et al., J Biol Chem 2003
:
Interaction between
Src and a C-terminal proline-rich motif of Akt is
required for
Akt activation ... We also showed that phosphorylation of Tyr-315 in
Akt induced by
Src or EGF is dependent on the integrity of this proline-rich motif
Esposito et al., J Biol Chem 2003
:
Protein kinase B activation by reactive oxygen species is independent of tyrosine kinase receptor phosphorylation and
requires SRC activity
Fukuda et al., Cancer Res 2003
(Colonic Neoplasms) :
In contrast, phosphorylation of
AKT is
dependent on ERK and
C-SRC activity
Lu et al., J Biol Chem 2003
(Breast Neoplasms) :
Activated
Src reduces the ability of PTEN to dephosphorylate phosphatidylinositols in micelles and
promotes AKT translocation to cellular plasma membranes but does not alter PTEN activity toward water-soluble phosphatidylinositols
Lopez et al., J Biol Chem 2003
:
TEL-M1 delocalization requires the kinase activity of
v-SRC and is not
induced by oncogenic RAS or
AKT
Cheng et al., FEBS Lett 2004
(Neoplasms, Experimental) :
Biochemical analysis revealed that the Cas SH3 domain selectively inhibited
v-Src stimulated activations of
AKT and JNK, but not ERK and STAT3
Duxbury et al., Cancer Res 2004
(Adenocarcinoma...) :
Differential expression of CEACAM6 modulates
Akt activity in a
c-Src dependent manner, and CEACAM6 overexpression appears to protect cells from cytochrome c-induced caspase 3 activation and apoptosis
Ichiki et al., Biochem Biophys Res Commun 2004
:
GM6001, a matrix metalloproteinase inhibitor, and PP2, a
Src family protein kinase inhibitor,
suppressed 15-d-PGJ2- and TZDs induced phosphorylation of EGF-R and PDGFbeta-R as well as activation of ERK1/2 and
Akt
Steinle et al., Exp Eye Res 2005
(Choroidal Neovascularization) :
BRL37344 treatment also increased choroidal endothelial cell invasion by 103 % above control values ; the invasion response was inhibited by PP2 (
Src inhibitor ), LY294002 ( PI3K inhibitor ),
Akt inhibitor ( Akt-I ) , and matrix metalloproteinase 2/9 inhibitor ( MMP-I )
Murillo et al., Oncogene 2005
:
The activation of
c-Src by TGF-beta1 is EGFR dependent and is
required for full
Akt phosphorylation and cell survival
Wu et al., Am J Physiol Lung Cell Mol Physiol 2005
:
Inhibition of p38,
Src , and EGFR kinases with pharmacological inhibitors markedly
reduces Akt phosphorylation induced by Zn2+
Mehdi et al., Antioxid Redox Signal 2005
:
H2O2 induced phosphorylation of ERK1/2 and
PKB requires tyrosine kinase activity of insulin receptor and
c-Src
Trevino et al., Cancer Res 2005
(Adenocarcinoma...) :
Inhibition of
c-Src activity
resulted in decreased phosphorylation of
Akt , p38, and extracellular signal regulated kinase ( Erk ) -1/2
Park et al., J Biol Chem 2005
:
Knockdown of Stat3 reduces
AKT1 expression
induced by
v-Src
Kim et al., Blood 2006
:
Selective G ( 12/13 ) activation resulted in Src kinase activation, and
Akt phosphorylation induced by costimulation of G ( 12/13 ) and Gi/Gz was
inhibited by a
Src kinase inhibitor but not by a Rho kinase inhibitor
Choudhury et al., Cell Signal 2006
:
Expression of constitutively active
c-Src increased
Akt activity to the same extent as with PDGF ... Constitutively active
c-Src augmented PDGF induced
Akt activity, thus contributing to Akt signaling
Díaz-Montero et al., Eur J Cancer 2006
(Osteosarcoma) :
PI3-K/Akt mediated anoikis resistance of human osteosarcoma cells
requires Src activation ... Furthermore, pharmacological inhibition of
Src resulted in a decrease of
Akt phosphorylation at Ser473
Winograd-Katz et al., Oncogene 2006
:
In this study, we report that Cisplatin activates
PKB/Akt in several cancer cell lines and that this activation is
mediated by EGFR,
Src and PI3-kinase ... In this study, we report that Cisplatin activates
PKB/Akt in several cancer cell lines and that this activation is
mediated by EGFR,
Src and PI3-kinase
Koga et al., Proc Natl Acad Sci U S A 2006
:
Hsp90 inhibition transiently activates Src kinase and promotes
Src dependent
Akt and Erk activation
Duong et al., Cancer Res 2006
(Breast Neoplasms) :
Mammalian two-hybrid assays revealed that
AKT enhanced both
SRC1 and GRIP1 recruitment to the ER beta-AF2 domain, and reporter gene analyses revealed that AKT and GRIP1 cooperatively potentiated ER beta mediated transcription to a level much greater than either factor alone
Park et al., Cancer Res 2006
(Glioblastoma...) :
In addition, inhibitors of epidermal growth factor receptor ( EGFR ; AG490 and AG1478 ),
Src ( PP2 ), and p38 ( SB203580 ), EGFR neutralizing antibody, and transfection of DN-Src and DN-p38 significantly
blocked IR-induced
Akt phosphorylation and MMP-2 secretion
Fleming et al., Endocrinology 2006
:
Interestingly, inhibition of
Src activation
blocked the ability of EGF, but not IGF-I, to activate
AKT
Azar et al., Can J Physiol Pharmacol 2006
:
In this study, we used pharmacological inhibitors to investigate the
role of receptor and
Src-family-PTKs in H2O2 induced
PKB phosphorylation
Jin et al., Cancer Res 2007
(Cell Transformation, Neoplastic) :
Suppression of
c-Src by RNA interference in NIH3T3-ETV6-NTRK3 cells
resulted in markedly decreased expression of cyclin D1 and suppression of activation of Ras-Erk1/2 and
PI3K-Akt
Sung et al., Neurochem Res 2007
(Anoxia...) :
Inhibitors of growth factor receptor ( AG1478 ) and
Src ( PP2 ) and the antioxidant N-acetylcysteine did not
affect activation of ERK and
Akt , while the Ras and Raf inhibitors inhibited activation of ERK, but not Akt
Matsui et al., Circulation 2007
(Ischemia) :
PI3-kinase is associated with vascular endothelial growth factor induced PYK2/Src complex, and inhibition of
Src blocked
Akt activation
Kim et al., Growth Factors 2007
:
The ERK activatin was inhibited by the
Src inhibitor and the
Akt activation was
inhibited by inhibitors of EGFR and Src
Abid et al., J Biol Chem 2007
:
The permissive role of NADPH oxidase on phosphoinositide
3-kinase-Akt-forkhead signaling is mediated at post-VEGF receptor levels and
involves the nonreceptor tyrosine kinase
Src
Jin et al., J Biol Chem 2008
(Cell Transformation, Neoplastic) :
Suppression of
c-Src by RNA interference in highly metastatic 4T1 mammary cancer cells, which express endogenous TrkC,
resulted in markedly decreased expression of cyclin D1 and suppression of activation of Ras-Erk1/2 and
PI3K-Akt
Kashiwagi et al., Biochem Biophys Res Commun 2008
(Lung Neoplasms) :
More specifically, T3E dependent inhibition of
Src induced
Akt activation contributed to suppression of cell survival under hypoxia, and the reduction of fibrinolytic factors such as plasminogen activator-1(PAI-1) via the decrease of hypoxia-inducible factor-2alpha by T3E led to inhibition of hypoxic invasion
Lin et al., Toxicol Appl Pharmacol 2008
:
LPS stimulated
Src , PYK2, EGFR, and Akt phosphorylation and VCAM-1 expression were
attenuated by the inhibitors of Src ( PP1 ), EGFR ( AG1478 ), PI3-K ( LY294002 and wortmannin ), and Akt ( SH-5 ), respectively, or transfection with siRNAs of Src or
Akt and shRNA of p110
Morisco et al., Cardiovasc Res 2008
(Cardiomegaly) :
beta-Adrenergic activation of
Akt is
mediated by
Src , which associates with the endocytosis machinery and is necessary and sufficient to mediate beta-adrenergic hypertrophy
Vojtechová et al., Neoplasia (New York, N.Y.) 2008
:
Disruption of the
Src kinase activity
results in substantial reduction of the phosphorylation and activity of the
Akt/protein kinase B (PKB), phosphorylation of tuberin ( TSC2 ), mammalian target of rapamycin (mTOR), S6K1, ribosomal protein S6, and eukaryotic initiation factor 4E-binding protein 4E-BP1
Slomiany et al., Inflammopharmacology 2008
:
Our findings demonstrate that leptin protection of salivary gland acinar cells against ethanol cytotoxicity involves
Src kinase
mediated parallel activation of MAPK/ERK and
Akt that result in up-regulation of the respective prostaglandin and nitric oxide synthase pathways
Gingerich et al., Neuropharmacology 2008
:
Finally, we demonstrate that Src kinase acts upstream of the PI3K/Akt pathway based on our finding that the selective
Src inhibitor, PP2 ( 10microM ),
blocked the increases in nNOS phosphorylation levels, NO production, and
PI3K/Akt activity induced by ERbeta activation
Yano et al., Proc Natl Acad Sci U S A 2008
(Bone Neoplasms...) :
Hsp90 inhibition transiently activates osteoclast Src kinase and promotes
Src dependent
Akt activation
Chabot et al., Mol Cell Biol 2009
:
The increased phosphorylation of
Src on Y529 under these conditions
results in impaired Src and
Akt activation ... Overall, our results reveal that despite its negative role on global VEGFR2 phosphorylation, DEP-1 is a positive regulator of VEGF mediated
Src and
Akt activation and endothelial cell survival
Kim et al., Mol Cancer Res 2008
(MAP Kinase Signaling System...) :
Inhibition of
c-Src attenuated Rac1 and p38 MAPK activations and Ser ( 473 ) phosphorylation of
Akt
Madeira et al., J Vasc Res 2009
(MAP Kinase Signaling System) :
This effect involves the intracellular formation of ROS in endothelial cells leading to the
Src kinase/phosphoinositide
3-kinase/Akt dependent phosphorylation of eNOS
Gates et al., Am J Physiol Gastrointest Liver Physiol 2009
:
Maximal cAMP-GEF mediated
Akt phosphorylation as well as protection from bile acid induced apoptosis
requires activation of
Src-TYK and the EGFR
Lodeiro et al., PloS one 2009
:
c-Src regulates
Akt signaling in response to ghrelin via beta-arrestin signaling independent and -dependent mechanisms ... In summary this work reveals that
c-Src is crucially
involved in the ghrelin mediated
Akt activation
Sun et al., Am J Physiol Heart Circ Physiol 2009
(Disease Models, Animal...) :
Taken together, we hypothesize that TSP1 antagonizes VEGF-driven Akt survival signaling in part through the recruitment of Fyn to membrane domains containing CD36, but when TSP1 is absent, an opposing
Src recruitment
contributes to VEGF-driven
Akt phosphorylation and capillary survival
Tian et al., J Biol Chem 2009
:
Mechanistically, both
Src and caveolin-1 are
required for ouabain induced activation of
Akt and up-regulation of Na/K-ATPase
Vlotides et al., Endocrinology 2009
:
Src inhibition with 4-amino-5- ( 4-chlorophenyl ) -7- ( t-butyl ) pyrazolo [ 3,4-d ] pyrimidine
suppressed FGF-2 induced
Akt and focal adhesion kinase, indicating effects downstream of FGF-2 induced Src activation
Meng et al., Br J Cancer 2009
(Adenocarcinoma...) :
In addition, the
Src inhibitor, PP2,
blocked the phosphorylation of FAK, ERK1/2, PI3K, and
Akt
Zhang et al., Cancer Cell 2009
(Bone Neoplasms...) :
Src mediates
AKT regulation and cancer cell survival responses to CXCL12 and TNF related apoptosis inducing ligand ( TRAIL ), factors that are distinctively expressed in the bone metastasis microenvironment
Fan et al., Anticancer Drugs 2010
:
SF protection against TRAIL required
c-Akt ; but unlike protection against adriamycin, it did not
require Src signaling or the classical pathway of nuclear factor-kappaB activation
Song et al., Cell Signal 2010
:
In this study, we report that
Src , c-Cbl, and PI3K are
involved in the phosphorylation of
Akt during TRAIL treatment
Hsu et al., Mol Nutr Food Res 2011
(Adenocarcinoma...) :
Inhibition of the
FAK/Src complex by glabridin also
blocked AKT and ERK1/2 activation, resulting in reduced activation of RhoA as well as myosin light chain phosphorylation
Wu et al., Cell Physiol Biochem 2010
:
Pressure activates
Src dependent
FAK-Akt and ERK1/2 signaling pathways in rat hepatic stellate cells
Tsai et al., Integr Cancer Ther 2011
(Carcinoma, Non-Small-Cell Lung...) :
Inhibition of the
FAK/Src complex by glabridin also
blocked Akt activation, resulting in reduced activation of RhoA and myosin light chain phosphorylation
Wang et al., J Cell Physiol 2011
:
Engagement of G ( i/o ) -- and G ( q ) -coupled ET ( B ) receptors by ET-1 led to activation of
c-Src dependent phosphoinositide 3-kinase
(PI3K)/Akt and p42/p44 mitogen activated protein kinase ( MAPK ) and then activated transcription factor nuclear factor-?B ( NF-?B )
Lei et al., Am J Physiol Lung Cell Mol Physiol 2011
:
In summary, in adult rat AECs T3-stimulated
Src kinase activity can
activate both
PI3K/Akt and MAPK/ERK1/2, and activation of Akt is necessary for T3-induced Na-K-ATPase activity
Liu et al., Exp Cell Res 2011
:
Inhibitors of epidermal growth factor (EGF) receptor tyrosine kinase and
Src attenuated insulin induced ERK and
Akt phosphorylation, as well as thymidine incorporation, whereas 2-deoxy-glucose incorporation was not affected by these inhibitors ... Mechanical stretch augments insulin induced VSMC proliferation via upregulation of IGF-1 receptor, and downstream
Src/EGF receptor
mediated ERK and
Akt activation
Chen et al., Cell Biol Int 2012
:
In addition, the
Src tyrosine kinase inhibitor, PP2,
blocked ISO mediated both
Akt and ERK activation and heavily suppressed viability
Feng et al., Oncogene 2012
(Disease Progression...) :
Inhibition of
Src by Src inhibitors
attenuated PDGF-A stimulated phosphorylation of
Akt and Dyn2 and glioma cell migration
Buitrago et al., J Cell Biochem 2012
:
Of relevance,
Src and PI3K are
involved in
Akt activation and in MHC and myogenin increased expression by 1a,25 ( OH ) ( 2 ) D ( 3 )
Rattmann et al., J Vasc Res 2012
:
Natural product extract of Dicksonia sellowiana induces endothelium dependent relaxations by a redox-sensitive
Src- and
Akt dependent
activation of eNOS in porcine coronary arteries
Feng et al., Biosci Biotechnol Biochem 2012
(Insulin Resistance) :
Palmitate contributes to insulin resistance through downregulation of the
Src mediated phosphorylation of
Akt in C2C12 myotubes ... Additionally, it inhibited the insulin stimulated phosphorylation of Src at Tyr416, causing a reduction in the
Src mediated phosphorylation of
Akt ... The findings indicate that palmitate contributes to insulin resistance by inhibiting the
Src mediated phosphorylation of
Akt in C2C12 myotubes, and this provides insight into the molecular mechanisms of FFA induced insulin resistance
Song et al., Journal of neuroinflammation 2012
(Neuroblastoma) :
We also found that
Src/PI3K/Akt inhibitors
prevented LLLT stimulated
Akt ( Ser473 and Thr308 ) phosphorylation and blocked Rac1 activity and actin based microglial phagocytosis, indicating the activation of Src/PI3K/Akt/Rac1 signaling pathway
Cho et al., Mol Biol Cell 2013
(Atherosclerosis) :
Apo(a) caused the disruption of VE-cadherin/ß-catenin complexes in a
Src dependent manner, decreased ß-catenin phosphorylation, and increased phosphorylation of
Akt and glycogen synthase kinase-3ß, ultimately resulting in increased nuclear translocation of ß-catenin ; all of these effects are downstream of apo(a) attenuation of phosphatase and tensin homologue deleted on chromosome 10 activity
Yang et al., J Biol Chem 2013
(Diabetes Mellitus...) :
The leucine facilitated insulin induced phosphorylation of
Akt at residue 473 was not affected by knocking down the key component of mTORC1 or -2 complexes but was
blocked by inhibition of
c-Src ( PP2 ), PI3K ( LY294002 ), Gai protein ( pertussis toxin or siRNA against Gai1 gene, or ß-arrestin 2 ( siRNA ) )
Li et al., Invest Ophthalmol Vis Sci 2013
(MAP Kinase Signaling System) :
Active PKCa phosphorylates
Src to
induce PI-3K to phosphorylate
AKT that subsequently activates the ERK1/2 cascade to stimulate goblet cell proliferation