◀ Back to RELA
PIK3R1 — RELA
Pathways - manually collected, often from reviews:
-
NCI Pathway Database IL1-mediated signaling events:
RelA (RELA)
→
IL1 beta fragment/IL1R1/IL1RAP/PI3K complex (IL1B-IL1R1-IL1RAP-PIK3CA-PIK3R1)
(modification, collaborate)
Sizemore et al., Mol Cell Biol 1999, Reddy et al., J Biol Chem 1997
Evidence: mutant phenotype, physical interaction
-
NCI Pathway Database Atypical NF-kappaB pathway:
NF kappa B1 p50/RelA complex (NFKB1-RELA)
→
I kappa B alpha/PIK3R1 complex (NFKBIA-PIK3R1)
(modification, collaborate)
Kang et al., Mol Cell Biochem 2003, Béraud et al., Proc Natl Acad Sci U S A 1999
Evidence: assay, physical interaction
-
NCI Pathway Database Atypical NF-kappaB pathway:
NF kappa B1 p50/RelA complex (NFKB1-RELA)
→
PI3K complex (PIK3CA-PIK3R1)
(modification, collaborate)
Kang et al., Mol Cell Biochem 2003, Béraud et al., Proc Natl Acad Sci U S A 1999
Evidence: assay, physical interaction
-
NCI Pathway Database Atypical NF-kappaB pathway:
I kappa B alpha/PIK3R1 complex (NFKBIA-PIK3R1)
→
NF kappa B1 p50/RelA/I kappa B alpha complex (NFKB1-NFKBIA-RELA)
(modification, collaborate)
Kang et al., Mol Cell Biochem 2003, Béraud et al., Proc Natl Acad Sci U S A 1999
Evidence: assay, physical interaction
-
NCI Pathway Database Atypical NF-kappaB pathway:
NF kappa B1 p50/RelA/I kappa B alpha complex (NFKB1-NFKBIA-RELA)
→
PI3K complex (PIK3CA-PIK3R1)
(modification, collaborate)
Kang et al., Mol Cell Biochem 2003, Béraud et al., Proc Natl Acad Sci U S A 1999
Evidence: assay, physical interaction
Text-mined interactions from Literome
Sizemore et al., Mol Cell Biol 1999
:
In contrast,
PI3K inhibitors
block the IL-1 stimulated phosphorylation of
NF-kappaB itself, especially the p65/RelA subunit
Ozes et al., Nature 1999
:
Wortmannin ( a PI(3)K inhibitor ), dominant negative
PI(3)K or kinase-dead Akt
inhibits TNF mediated
NF-kappaB activation
Madrid et al., Mol Cell Biol 2000
:
In this study, we show that oncogenic H-Ras
requires PI3K and Akt to stimulate the transcriptional activity of
NF-kappaB
Kim et al., FEBS Lett 2000
:
This study shows a direct evidence that the SH2-SH2-SH3 region of PLCgamma1 contributes to the NF-kappaB signaling and that MAPK, but not
PI3K and PKC, is
involved in SH2-SH2-SH3 mediated
NF-kappaB activation in these cells
Burow et al., Biochem Biophys Res Commun 2000
:
PI3K and Akt
stimulated NF-kappaB activation in a dose dependent manner, suggesting a common link between these two pathways ...
PI3K-Akt signaling
activated NF-kappaB through both TNFR signaling dependent and -independent mechanisms, potentially representing a mechanism by which Akt functions to suppress apoptosis in cancer
Wooten et al., Mol Cell Biol 2000
:
Src,
PI3K , and PKC-iota were likewise
required for NGF induced
NF-kappaB activation and cell survival, whereas Ras was not required for either survival or NF-kappaB activation but was required for differentiation
Baumgartner et al., Cell Microbiol 2000
:
PI3-K induction of GM-CSF appears to be at the transcriptional level and, consistently, we demonstrate that
PI3-K is also
involved in the constitutive induction of AP-1 and
NF-kappaB , which characterizes Theileria infected leucocytes
Reyes-Reyes et al., J Cell Sci 2001
(Leukemia) :
We found that integrins activated both
NF-kappaB and MAPK in a
PI 3-K dependent manner, as wortmannin and LY294002 blocked these responses
Johnson et al., J Virol 2001
:
The cellular kinases Akt and p70S6K and the transcription factor
NF-kappaB were activated in a
PI3-K dependent manner at similar times following HCMV infection
Thomas et al., J Biol Chem 2002
:
Finally, both
PI 3-K inhibition by LY294002 and AKT inhibition by transfection of a dominant negative enzyme
blocked RSV induced
NF-kappaB transcriptional activity
Reyes-Reyes et al., Biochem J 2002
:
However,
PI-3K was
required for beta1 integrin-, but not beta2 integrin-, mediated
NF-kappaB activation
Shah et al., J Gastrointest Surg 2001
(Adenocarcinoma...) :
NF-kappaB dependent gene expression, however, was ultimately suppressed by Ly294002, suggesting that
PI3k dependent activation of
NF-kappaB is IkappaBalpha independent
Gingery et al., J Cell Biochem 2003
(MAP Kinase Signaling System) :
PI3K inhibition also
blocked MEK1/2, ERK1/2, and AKT phosphorylation and
NFkappaB activation in purified osteoclasts
St-Germain et al., Molecular cancer 2004
(Endometrial Neoplasms) :
Inhibition of
PI 3-K with Wortmannin and LY294002 blocked IkappaB phosphorylation,
reduced NF-kappaB nuclear activity, reduced COX-2 expression and induced apoptosis
Philpott et al., Proc Natl Acad Sci U S A 2004
:
We propose that integrin mediated
PI3K induction of
NF-kappaB activates an autocrine TNF-alpha pathway required for DC maturation in response to Ad
Strassheim et al., J Immunol 2004
(Inflammation) :
PI3-K blockade did not
inhibit nuclear translocation of
NF-kappa B , but did prevent Ser ( 536 ) phosphorylation of the p65 subunit of NF-kappa B, an event required for maximal transcriptional activity of NF-kappa B
Jang et al., Biochem Biophys Res Commun 2004
(Adenocarcinoma) :
Specifically, IL-1beta induced nuclear translocation of NF-kappaB was in part attenuated by LY294002, but not by GF109203X, SB203580, and SP600125, suggesting
PI3K dependent nuclear translocation of
NF-kappaB in response to IL-1beta
Ahn et al., Cell Physiol Biochem 2005
:
Wortmannin inhibited NF-kappaB binding and transcriptional activity without inhibiting NF-kappaB translocation to the nucleus, indicating that
PI3K/Akt signaling
activates NF-kappaB transcriptional activity directly
Jang et al., Cell Signal 2005
:
Interestingly, there was
PI3K dependent
activation of AKT, p70S6K, JNKs, and
NF-kappaB in response to catalase
Aksoy et al., Eur J Immunol 2005
:
In the same models of DC activation,
PI3K inhibition
increased DNA binding activity of
NF-kappaB , but not interferon response factor (IRF)-3, the key transcription factors required for TLR mediated IFN-beta synthesis ... Furthermore, wortmannin
enhanced NF-kappaB activity induced by TRIF overexpression in HEK 293T cells, while overexpression of catalytically active
PI3K selectively attenuated TRIF mediated NF-kappaB transcriptional activity ... We conclude that inhibition of
PI3K activity
enhances TRIF dependent
NF-kappaB activity, and thereby increases IFN-beta synthesis elicited by TLR3 or TLR4 ligands
Chang et al., Microbes Infect 2006
:
Flavivirus induces interferon-beta gene expression through a pathway involving RIG-I dependent IRF-3 and
PI3K dependent
NF-kappaB activation
Sugimori et al., J Bone Miner Metab 2005
:
BMP-2 prevents apoptosis of the N1511 chondrocytic cell line through
PI3K/Akt mediated
NF-kappaB activation ... Thus, BMP-2 induced
NF-kappaB activation is
mediated by
PI3K/Akt signaling
Ko et al., FEBS Lett 2005
:
Furthermore, PAF induced
NF-kappaB activation was blocked by selective inhibitors of Ca ( 2+ ),
PI3K , or extracellular signal regulated kinase ( ERK ) ... Our results suggest that PAF induced MMP-9 expression, in a
NF-kappaB dependent manner, is regulated by Ca ( 2+ ),
PI3K and ERK signaling pathways
Hsieh et al., J Cell Physiol 2006
:
Moreover, S1P stimulated activation of NF-kappaB promoter activity was blocked by phosphatidylinositol 3-kinase (PI3K) inhibitor LY294002 and helenalin, but not by U0126, suggesting that
involvement of
PI3K/Akt in the activation of
NF-kappaB
Al-Rasheed et al., J Am Soc Nephrol 2006
(Diabetic Nephropathies) :
Phosphatidylinositol 3-kinase but not extracellular signal regulated mitogen activated protein kinase
mediated C-peptide and insulin activation of
NF-kappaB
Frey et al., J Biol Chem 2006
:
Phosphatidylinositol 3-kinase gamma signaling through protein kinase Czeta
induces NADPH oxidase mediated oxidant generation and
NF-kappaB activation in endothelial cells
Hennig et al., J Nutr Biochem 2006
(Inflammation) :
Furthermore, inhibition of ERK activity by PD98059 and
PI3K/Akt activity by LY294002 or wortmannin significantly
reduced the LA-induced activation of
nuclear factor kappa B (NF-kappaB)
Sanchez-Lockhart et al., J Immunol 2006
:
CD28 signaling through
PI3K results in the recruitment of protein kinase C (PKC)theta to the cSMAC,
activation of
NF-kappaB , and induction of IL-2 transcription
Choi et al., Int Immunopharmacol 2006
:
However, many aspects of the
PI3K negative
regulation of
NF-kappaB activation remain to be clarified ... The present study was conducted to shed light on cell-type specificity, stimulus specificity, and upstream mechanisms of the enhanced
NF-kappaB activation by
PI3K inhibitors
Kuo et al., J Immunol 2006
:
Our results reveal that class III PI3K specifically regulates CpG oligodeoxynucleotide ( ODN ) -induced cytokine and NO production as well as NF-kappaB activation, whereas class I
PI3K regulates both CpG ODN- and LPS induced IL-12 production and
NF-kappaB activation
Parsa et al., PLoS Pathog 2006
(Gram-Negative Bacterial Infections) :
Inhibition of
PI3K/Akt resulted in suppression of F. novicida
induced cytokine production through the inhibition of
NFkappaB
Kim et al., Biochem Biophys Res Commun 2006
:
Involvement of HDAC1 and the
PI3K/PKC signaling pathways in
NF-kappaB activation by the HDAC inhibitor apicidin
Benson et al., Eur J Immunol 2006
:
Rapid CD40 rescue did not require
NF-kappaB activation and was independent of de novo protein synthesis, but was
dependent upon active
PI3 K
Hwang et al., Carcinogenesis 2007
:
Taken together, 9Z,11E-CLA
inhibits NF-kappaB driven-COX-2 expression by blocking the IKK and
PI3K-Akt signaling in TPA treated hairless mouse skin in vivo, which may account for its previously reported anti-tumor promoting effects
Parhar et al., Mol Cell Biochem 2007
:
p65 (
Rel A ) Ser536 phosphorylation was not
affected by the
PI3K inhibitors but was dose-dependently attenuated by TPCK
Zhande et al., Am J Physiol Heart Circ Physiol 2007
:
EPO caused a prolonged activation of
nuclear factor (NF)-kappaB , which was
blocked by inhibition of
PI3K , but not by inhibition of mitogen activated protein ( MAP ) /ERK kinase ( MEK ), suggesting that EPO activated NF-kappaB requires PI3K activity
Kanda et al., Eur J Immunol 2007
:
Inhibitors of
PI3 K , p38 MAPK, and MEK
suppressed IL-18 plus IFN-gamma induced CXCL9, CXCL10, and CXCL11 production and
NF-kappaB , STAT1, and IRF-1 activities
Nakamura et al., Rheumatol Int 2007
(Sjogren's Syndrome) :
Chemical inhibition of
PI3K-Akt by LY294002/wortmannin did not affect EGF mediated NF-kappaB p65 nuclear translocation ; and
NF-kappaB inhibition by Bay 11-7082 did not
suppress Akt phosphorylation
Belaiba et al., Mol Biol Cell 2007
(Anoxia) :
Together, these findings provide a novel mechanism in which hypoxia induces HIF-1alpha mRNA expression via the
PI3K/AKT pathway and
activation of
NFkappaB
Kim et al., J Immunol 2007
(Asthma...) :
Our results also showed that
PI3K inhibitors or AdPTEN
down-regulated a transcription factor,
NF-kappaB activity, and BAY 11-7085 substantially reduced the increased levels of IL-17 after TDI inhalation
Kwon et al., Biochem Biophys Res Commun 2008
:
Moreover, inhibitors of Ras ( sulindac sulfide and farnesyltransferase inhibitor I ) or
PI3K/Akt ( wortmannin ),
reduced the amounts of Akt1 and Ki-Ras in the nucleus as well as partial
NF-kappaB activity
Reddy et al., J Cell Physiol 2008
:
Interleukin-18 stimulates fibronectin expression in primary human cardiac fibroblasts via
PI3K-Akt dependent
NF-kappaB activation
Liu et al., Cell Microbiol 2008
(Coxsackievirus Infections...) :
Furthermore, silencing NF-kappaB with siRNAs significantly inhibited the phosphorylation of FAK and Akt, but not their total expression levels, indicating that
NF-kappaB activation is
required for the IGTP induced activation of FAK and
PI3K/Akt
García et al., Leuk Res 2009
(Lymphoma) :
PI3K/Akt inhibition modulates multidrug resistance and
activates NF-kappaB in murine lymphoma cell lines
Matsuda et al., Blood 2009
:
Nevertheless, both
PI3K and Btk are
required for the activation of
NF-kappaB , a critical transcription factor family for B-cell development and function
Graham et al., Prostate 2009
(Neoplasm Metastasis...) :
PI3K/Akt dependent transcriptional regulation and activation of BMP-2-Smad signaling by
NF-kappaB in metastatic prostate cancer cells
Méndez-Samperio et al., Cell Immunol 2009
:
Finally, the inhibition of
PI3K affect
NF-kB activation in M. bovis BCG infected cells, indicating that PI3K activity is required for the M. bovis BCG induced activation of NF-kB
Takeshima et al., BMC microbiology 2009
(Helicobacter Infections) :
PI3K inhibitor suppressed H. pylori
induced p65 phosphorylation and
NF-kappaB transactivation, as well as interleukin-8 expression
Kok et al., Trends Biochem Sci 2009
(Neoplasms) :
Recently identified mechanisms that control PI3K production include increased gene copy number in cancer, and transcriptional
regulation of the p110alpha
PI3K gene by FOXO3a,
NF-kappaB and p53, and of the PI3K regulatory subunits by STAT3, EBNA-2 and SREBP
Jiang et al., J Hepatol 2009
:
The JAK/STAT- and
PI3K/Akt dependent pathways,
NF-kappaB activation and expression of the anti-apoptotic proteins Mcl-1 and A1 were evaluated
Bai et al., Int J Cancer 2009
(Cell Transformation, Neoplastic) :
The data further support the conclusion that
NFkappaB activity is
essential for
PI3K- and Akt induced oncogenic transformation
Wu et al., Glia 2010
(Gliosis) :
LPS triggered upregulation of CHL1 expression mediated through translocation of nuclear factor kappaB (NF-kappaB) to the nucleus is blocked by a specific
NF-kappaB inhibitor and by
inhibition of
PI3K , PKCdelta, and ERK1/2 activities, implicating NF-kappaB as a downstream target for upregulation of CHL1 expression
Han et al., Molecular cancer 2010
(Disease Models, Animal...) :
Co-treatment with
NF-kappaB , STAT3 or/and
PI3K inhibitors led to additive inhibition of iMyc E mu-1 cell proliferation, suggesting that these signaling pathways converge
Wang et al., J Biol Chem 2010
:
Shear induced interleukin-6 synthesis in chondrocytes : roles of E prostanoid ( EP ) 2 and EP3 in cAMP/protein kinase A- and
PI3-K/Akt dependent
NF-kappaB activation
Chen et al., J Biol Chem 2010
(Colorectal Neoplasms) :
rHSP90alpha induced the activities of ERK,
PI3K/Akt , and NF-kappaB p65, but only
NF-kappaB activation was
involved in HSP90alpha induced integrin alpha(V) expression
Gong et al., Biol Pharm Bull 2010
(Pancreatic Neoplasms) :
Activation of p65
NF-kappaB was
dependent on the phosphorylation of
PI3K/Akt
Di Santo et al., Journal of thrombosis and haemostasis : JTH 2011
(Thrombosis) :
The results demonstrated that, in MN interacting with activated PLT : ( i ) TF activity, antigen and mRNA were low until 8-10 h and dramatically increased thereafter, up to 24 h ; ( ii ) according to the kinetics of TF expression in MN, GSK3ß undergoes phosphorylation on serine 9, a process associated with down-regulation of enzyme activity ; ( iii ) pharmacological blockade of GSK3 further increased TF expression and was accompanied by increased accumulation of
NF-kB , in the nucleus ; ( iv ) blockade of phosphoinositide-3 kinase ( PI(3)K ) by wortmannin inhibited PLT induced TF expression ; and ( v ) according to the established role of the GSK3 downstream insulin receptor, insulin increased PLT induced TF expression in a
PI(3)K dependent manner
Xiong et al., Genome Res 2012
(Crohn Disease...) :
The analysis of two human diseases, glioblastoma and Crohn 's disease, detected abnormalities in previously identified disease associated pathways, such as pathways related to
PI3K signaling, DNA damage response, and the
activation of
NFKB