PI3K-AKT-NFKB pathway (Rattus norvegicus)

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TRANSCRIPTION FACTORSNUCLEAUSCELL ADHESION MOLECULESCELL MEMBRANEReactive oxygen speciesHeat shockANTI-APOPTOSISGROWTH FACTORSDirect inhibitionANTIGEN PROCESSINGProteosomal digestionIndirect activationAPOPTOSISDirect activationCYTOKINESIndirect inactivationSTRESS RESPONSE GENESCYTOPLASMDNAAkt2Bmp2Nfkb2IkkaBcl2Bnip3Ripk1MycVcamIcam-1HMOX1PdgfAPpp2r5dUbNfkb1Nfkb1Ppp2r3aEGFTraf6IL-1 RTNFBirc3CflipTraf2Ptk2Psmb9IkkbPik3r1Irs1Nfkbiecxcl2FasFth1TraddBaxIrs2EgfrNfkb2Erbb2HSPBmp3Fox01Ppp2caGlut1Irf1Tab1Ccl17BaxBimSod1ELAM-1RelATlr 4RelTapbpGlut2Gab2Tap1Ins1Sod2Bcl2l1RelAUbRantesCfbRas (KRAS)Tak1CXCL11Tpl-2IkkgcJunTirapTnfr1aBcl2A1Pdpk1RelAp53Pfkfb2NfkbiaMdm2InsrIgfbp2mTorAbca1NfkbibBcl2l10Glut4Akt1Myd88c-FosGsk-3Pik3caIrak4Birc2BadRelA


Description

NFKB is an important transcription factor induced by multiple cellular mechanisms. This pathway diagram depicts the major activators of the pathway and the downsteam genes regulated by the pathway. Activation of growth factor receptors by growth factors or cellular stress leads to the activation of the Phosphatidyl Inositol-3 kinases (PI3Kinases). PI3 kinases phosphorylate the inositol ring of Phosphatidyl inositol to produce Phosphatidyl inositol (3,4,5)-trisphosphate (PIP3). PIP3 activates downstream serine-threonine protein kinases such as Protein kinase B (AKT/PKB) through the kinase PDK1. Activation of Akt is tightly regulated by the quantity of the second messenger phosphatidyl inositol triphosphate.(PIP3). AKT itself can be dephosphorylated by the action of protein phosphatases. AKT contributes to several cellular functions including inhibition of apoptosis and cell survival, nutrient metabolism, cell growth, transcriptional regulation. AKT inhibits apoptosis by the phosphorylated inhibition of BAD and caspase 9. AKT phosphorylates and inactivates the enzyme glycogen synthetase kinase 3 and activates the transcription of glucose transporter (GLUT 1) and the glycolytic enzyme Phospho-fructo-2-kinase. AKT activates the NFΚΒ pathway through direct activation of IΚK and through phosphorylation of the MAP3kinase Tpl2. Activation of the NFΚΒ pathway also occurs through trans-membrane receptor complexes (TNF receptor superfamily, IL-1 receptor and the Toll like receptor family). Hypoxia, reactive oxygen species and cytokines such as TNF alpha and IL-1 activate the NFΚΒ pathway through these receptors. NFΚΒ elements are usually present in the cytoplasm as homo or heterodimers. They are localised to the cytoplasm by being complexed to proteins called the Inhibitors of Kappa beta (IΚΒ). Activation of the NFΚΒ pathway involves the breakdown of these complexes by proteosomal degradation of the IΚΒ subunits and translocation of the NFΚΒ elements into the nucleus. This is catalyzed by the action of protein kinases called the inhibitors of kappa kinase (IΚK) complex. In the nucleus NFΚΒ elements induce the transcription of genes related to cytokines, cell surface receptors, pro-apoptotic and anti-apoptotic proteins, adhesion molecules and anti-oxidants. NFΚΒ pathway is regulated by several feedback loops including increased transcription of the Iκβε gene in response to NFΚΒ activation.

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History

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CompareRevisionActionTimeUserComment
89860view12:28, 6 October 2016MkutmonModified description
87308view20:56, 20 July 2016EgonwAdded a bunch of Ensembl gene IDs.
87194view09:48, 19 July 2016EgonwAdded a bunch of Ensembl gene IDs.
87193view09:41, 19 July 2016EgonwModified title
83996view10:32, 9 January 2016EgonwAdded Ensembl identifiers (needs more)
83941view23:43, 4 January 2016MaintBotminor layout
71832view19:37, 18 October 2013MaintBotremoved data source from nodes without identifier
67596view11:31, 26 June 2013DdiglesOntology Term : 'phosphatidylinositol 3-kinase-Akt signaling pathway' added !
58950view18:19, 21 February 2013MaintBotUpdated Ensembl data source
41698view02:37, 2 March 2011MaintBotRemoved redundant pathway information and comments
36258view20:01, 14 March 2010AlexanderPicoModified categories
36254view19:52, 14 March 2010AlexanderPicoConnected lines and created groups
36253view21:25, 13 March 2010CoolseenuModified description
36252view21:19, 13 March 2010CoolseenuNew pathway

External references

DataNodes

View all...
NameTypeDatabase referenceComment
Abca1GeneProductENSRNOG00000018126 (Ensembl)
Akt1GeneProduct24185 (Entrez Gene)
Akt2GeneProduct25233 (Entrez Gene)
BadGeneProduct64639 (Entrez Gene) http://www.ncbi.nlm.nih.gov/gene/64639?ordinalpos=3&itool=EntrezSystem2.PEntrez.Gene.Gene_ResultsPanel.Gene_RVDocSum
BaxGeneProductENSRNOG00000020876 (Ensembl)
Bcl2A1GeneProductENSRNOG00000047606 (Ensembl)
Bcl2GeneProductENSRNOG00000002791 (Ensembl)
Bcl2l10GeneProduct114552 (Entrez Gene)
Bcl2l1GeneProduct24888 (Entrez Gene)
BimGeneProduct64547 (Entrez Gene)
Birc2GeneProductENSRNOG00000010602 (Ensembl)
Birc3GeneProduct78971 (Entrez Gene)
Bmp2GeneProductENSRNOG00000021276 (Ensembl)
Bmp3GeneProductENSRNOG00000002381 (Ensembl)
Bnip3GeneProductENSRNOG00000017243 (Ensembl)
CXCL11GeneProductENSRNOG00000022298 (Ensembl)
Ccl17GeneProductENSRNOG00000016278 (Ensembl)
CfbGeneProduct294257 (Entrez Gene) http://www.ncbi.nlm.nih.gov/gene/294257?ordinalpos=6&itool=EntrezSystem2.PEntrez.Gene.Gene_ResultsPanel.Gene_RVDocSum
CflipGeneProductENSRNOG00000012473 (Ensembl)
EGFGeneProductEGF
ELAM-1GeneProduct25544 (Entrez Gene)
EgfrGeneProductENSRNOG00000004332 (Ensembl)
Erbb2GeneProductENSRNOG00000006450 (Ensembl)
FasGeneProduct246097 (Entrez Gene) http://www.ncbi.nlm.nih.gov/gene/246097?ordinalpos=5&itool=EntrezSystem2.PEntrez.Gene.Gene_ResultsPanel.Gene_RVDocSum
Fox01GeneProduct84482 (Entrez Gene)
Fth1GeneProduct25319 (Entrez Gene) http://www.ncbi.nlm.nih.gov/gene/25319?ordinalpos=3&itool=EntrezSystem2.PEntrez.Gene.Gene_ResultsPanel.Gene_RVD
Gab2GeneProductENSRNOG00000011882 (Ensembl)
Glut1GeneProductENSRNOG00000008376 (Ensembl)
Glut2GeneProductENSRNOG00000011875 (Ensembl)
Glut4GeneProduct25139 (Entrez Gene) http://www.ncbi.nlm.nih.gov/gene/25139?ordinalpos=3&itool=EntrezSystem2.PEntrez.Gene.Gene_ResultsPanel.Gene_RVDocSum
Gsk-3GeneProduct50686 (Entrez Gene) http://www.ncbi.nlm.nih.gov/gene/50686?ordinalpos=2&itool=EntrezSystem2.PEntrez.Gene.Gene_ResultsPanel.Gene_RVDocSum
HMOX1GeneProductENSRNOG00000014117 (Ensembl)
HSPGeneProduct
IL-1 RGeneProduct25663 (Entrez Gene) http://www.ncbi.nlm.nih.gov/gene/25663?ordinalpos=3&itool=EntrezSystem2.PEntrez.Gene.Gene_ResultsPanel.Gene_RVDocSum
Icam-1GeneProductENSRNOG00000020679 (Ensembl)
Igfbp2GeneProductENSRNOG00000016957 (Ensembl)
IkkaGeneProduct309361 (Entrez Gene) http://www.ncbi.nlm.nih.gov/gene/309361?ordinalpos=4&itool=EntrezSystem2.PEntrez.Gene.Gene_ResultsPanel.Gene_RVDocSum
IkkbGeneProduct84351 (Entrez Gene)
IkkgGeneProduct309295 (Entrez Gene)
Ins1GeneProductENSRNOG00000012052 (Ensembl)
InsrGeneProductENSRNOG00000029986 (Ensembl)
Irak4GeneProduct300177 (Entrez Gene)
Irf1GeneProduct24508 (Entrez Gene) http://www.ncbi.nlm.nih.gov/gene/24508?ordinalpos=4&itool=EntrezSystem2.PEntrez.Gene.Gene_ResultsPanel.Gene_RVDocSum
Irs1GeneProduct25467 (Entrez Gene)
Irs2GeneProduct29376 (Entrez Gene)
Mdm2GeneProduct314856 (Entrez Gene) http://www.ncbi.nlm.nih.gov/gene/314856?ordinalpos=5&itool=EntrezSystem2.PEntrez.Gene.Gene_ResultsPanel.Gene_RVDocSum
MycGeneProductENSRNOG00000004500 (Ensembl)
Myd88GeneProductENSRNOG00000013634 (Ensembl) http://www.ncbi.nlm.nih.gov/gene/301059?ordinalpos=3&itool=EntrezSystem2.PEntrez.Gene.Gene_ResultsPanel.Gene_RVDocSum
Nfkb1GeneProductENSRNOG00000023258 (Ensembl)
Nfkb2GeneProductENSRNOG00000019311 (Ensembl)
NfkbiaGeneProductENSRNOG00000007390 (Ensembl)
NfkbibGeneProductENSRNOG00000020063 (Ensembl)
NfkbieGeneProduct316241 (Entrez Gene) http://www.ncbi.nlm.nih.gov/gene/316241?ordinalpos=2&itool=EntrezSystem2.PEntrez.Gene.Gene_ResultsPanel.Gene_RVDocSum
PdgfAGeneProduct25266 (Entrez Gene)
Pdpk1GeneProduct81745 (Entrez Gene) http://www.ncbi.nlm.nih.gov/gene/81745?ordinalpos=3&itool=EntrezSystem2.PEntrez.Gene.Gene_ResultsPanel.Gene_RVDocSum
Pfkfb2GeneProductENSRNOG00000004162 (Ensembl)
Pik3caGeneProduct170911 (Entrez Gene)
Pik3r1GeneProduct25513 (Entrez Gene)
Ppp2caGeneProductENSRNOG00000005389 (Ensembl)
Ppp2r3aGeneProductENSRNOG00000022999 (Ensembl)
Ppp2r5dGeneProductPPP2R5D
Psmb9GeneProductENSRNOG00000000459 (Ensembl)
Ptk2GeneProductENSRNOG00000007916 (Ensembl) http://www.ncbi.nlm.nih.gov/gene/5747?ordinalpos=2&itool=EntrezSystem2.PEntrez.Gene.Gene_ResultsPanel.Gene_RVDocSum
RantesGeneProduct81780 (Entrez Gene)
Ras (KRAS)GeneProductENSRNOG00000009338 (Ensembl)
RelGeneProduct305584 (Entrez Gene) http://www.ncbi.nlm.nih.gov/gene/305584?ordinalpos=10&itool=EntrezSystem2.PEntrez.Gene.Gene_ResultsPanel.G
RelAGeneProductENSRNOG00000030888 (Ensembl)
Ripk1GeneProduct306886 (Entrez Gene)
Sod1GeneProductENSRNOG00000002115 (Ensembl)
Sod2GeneProductENSRNOG00000019048 (Ensembl)
TNFGeneProductENSRNOG00000000837 (Ensembl)
Tab1GeneProduct25663 (Entrez Gene) http://www.ncbi.nlm.nih.gov/gene/315139?ordinalpos=5&itool=EntrezSystem2.PEntrez.Gene.Gene_ResultsPanel.Gene_RVDocSum
Tak1GeneProduct313121 (Entrez Gene) http://www.ncbi.nlm.nih.gov/gene/313121?ordinalpos=8&itool=EntrezSystem2.PEntrez.Gene.Gene_ResultsPanel.Gene_RVDocSum
Tap1GeneProductENSRNOG00000000457 (Ensembl)
TapbpGeneProduct25217 (Entrez Gene) http://www.ncbi.nlm.nih.gov/gene/25217?ordinalpos=3&itool=EntrezSystem2.PEntrez.Gene.Gene_ResultsPanel.Gene_RVDocSum
TirapGeneProduct680127 (Entrez Gene) http://www.ncbi.nlm.nih.gov/gene/680127?ordinalpos=3&itool=EntrezSystem2.PEntrez.Gene.Gene_ResultsPanel.Gene_RVDocSum
Tlr 4GeneProduct29260 (Entrez Gene)
Tnfr1aGeneProduct25625 (Entrez Gene) http://www.ncbi.nlm.nih.gov/gene/25625?ordinalpos=4&itool=EntrezSystem2.PEntrez.Gene.Gene_ResultsPanel.Gene_RVDocSum
Tpl-2GeneProduct116596 (Entrez Gene) http://www.ncbi.nlm.nih.gov/gene/116596?ordinalpos=2&itool=EntrezSystem2.PEntrez.Gene.Gene_ResultsPanel.Gene_RVDo
TraddGeneProductENSRNOG00000015179 (Ensembl)
Traf2GeneProduct311786 (Entrez Gene) http://www.ncbi.nlm.nih.gov/gene/311786?ordinalpos=4&itool=EntrezSystem2.PEntrez.Gene.Gene_ResultsPanel.Gene_RVDocSum
Traf6GeneProduct311245 (Entrez Gene) http://www.ncbi.nlm.nih.gov/gene/311245?ordinalpos=4&itool=EntrezSystem2.PEntrez.Gene.Gene_ResultsPanel.Gene_RVDocSum
UbGeneProductENSRNOG00000000768 (Ensembl)
UbGeneProductENSRNOG00000057823 (Ensembl)
VcamGeneProductENSRNOG00000014333 (Ensembl)
c-FosGeneProductENSRNOG00000008015 (Ensembl)
cJunGeneProductENSRNOG00000026293 (Ensembl)
cxcl2GeneProduct114105 (Entrez Gene) http://www.ncbi.nlm.nih.gov/gene/114105?ordinalpos=3&itool=EntrezSystem2.PEntrez.Gene.Gene_ResultsPanel.Gene_RVDocSum
mTorGeneProduct56718 (Entrez Gene) http://www.ncbi.nlm.nih.gov/gene/56718?ordinalpos=2&itool=EntrezSystem2.PEntrez.Gene.Gene_ResultsPanel.Ge
p53GeneProduct24842 (Entrez Gene) http://www.ncbi.nlm.nih.gov/gene/24842?ordinalpos=9&itool=EntrezSystem2.PEntrez.Gene.Gene_ResultsPanel.Gen

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