Focal adhesion: PI3K-Akt-mTOR signaling pathway (Mus musculus)

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1-17Integrin alpha (ITGA)PIP3+pIntegrin beta (ITGB)ECM-Receptor InteractionsNuclear to Cytoplasm Translocation-pCytokineRVEGF Siganling/AngiogenesisCytokine+pLamc3IbspItga11Itgb2Ifnar2VtnLama2Pik3cbDdit4Lamb2Il2rgIfnar1Col1a1Col4a1Thbs3Itga5Jak1Pik3caCol5a1Thbs1ItgavIl4raIfna1Col1a2Il3raSpp1Il2raAkt3Itgb4RelnItga3Il6raLama5GhrCol11a2Itga8Itgb6Itgb7Il2rbCol5a2Pik3r4LOC235580Ifna2Itga7EporItgb5ItgaeItgamCol4a6Pik3cdCol6a2ItgalItgadCol11a1Grb2Tsc2Col2a1Itga4Lamc1ChadItgb8PrlrCol4a2Itgb1Lamc2TnnCsf3rItga6TnxbAkt1EpoIfna11Lamb1-1TnrCol5a3Itga2bItga10Il7rTsc1Jak2PeloPik3r1PtenPtk2Pik3ip1Stk11Itga9Sos1CompOsmrLama3Col4a4ItgaxCol3a1Thbs2Lamb3TncLama4Csf3Thbs4VwfJak3Lama1Pik3r2GhItga2Akt2Itgb3Fn1Pik3r5Efna1FgfFgf11Fgf10Efna2EgfFgf12Csf1Angpt4Angpt2Angpt1VegfaEfna3Efna4Efna5Fgf14Fgf13Fgf15Fgf17Fgf18Fgf2Fgf3Fgf4Fgf6Fgf7Fgf8Fgf9FigfHgfIfg1Ins1Ins2KitlKik1b4Kik1b4VegfcVegfbPdgfbPgfPdgfaNgfPdgfcFgf21Fgf23Fgf22PdgfdFgf20Fgf16Growth FactorFgfr2KdrInsrFgfr3Igf1rKitFgfr1Epha2EgfrCsf1rFgfr4Flt1Flt4NgfrMetPdgfraPdgfrbTekRTKIrs1Akt1s1Ifna4Ifna5Ifna6Ifna7Ifna9IfnabIfnb1Il2OsmPrlIfna13Gm12597Ifna12Ifna14MAPK Signaling PathwayChrm1Lpar1F2rChrm2Lpar5Lpar2Lpar3Lpar6Lpar4GPCRGm15776Gnb2Gnb1Gm5741Gnb4Gngt1Gng10Gng12Gnb3GByGng2Gng3Gng4Gng5Gng7Gng8Gngt2Gng13Gng11Pik3cgNrasKrasHrasChemokines, Homones, NeurotransmittersPI3K (class IA)PI3K (class IB)HypoxiaEnergy StressStradaCab39Cab39lPrkaaPrkaa2Mlst8RhebMtorRptorAMPKmTORHif1aUlk1Crtc2Cdc37Hsp90ab1Phllp1Tcl1Pdk1Gm2436Ppp2cbPpp2caGm2446Ppp2r5dPpp2r5bPpp2r2bPpp2r1bPpp2r3dPpp2r3aPpp2r5cPpp2r5ePpp2r2cPpp2r1aPpp2r2dppp2r5aPpp2r3cHsp90aa1Hsp90b1Phlpp2Mtcp1Tcl1b1Tcl1b4PP2ARaf1Mapk2k2Map2k1Mapk1Mapk3Gsk3bFoxo3Foxo1IkbkbBadCasp9Mdm2IkbkgCdkn1bCdkn1aAtf2Creb3Creb1Atf4Creb3l2Creb3l3Atf6bCreb3l1Creb3l4Creb5Nos3AMP/ATP or ADP/ATPMetforminAICAR+p+p+p+p+p+pTbc1d1Rab8aRab2aRab10Rab11bRab14Slc2a4Slc2a1Slc2a3Slc2a2GLUTPpargc1aDNAGys1Gys2Pfkfb2Pfkfb1Pfkfb3Pfkfb4LipeSrebf1HmgcrAcacaCell SurvivalCell CycleAutophagyCell Growth & Protein SynethesisFatty Acid BiosynthesisCholesterol synthesisGlycogen synthesisGlycolysis/GluconeogenesisCell ProliferationAngiogenesisDNA repairGlycolysis/GluconeogenesisLypolysisElavl1Nos1Nos2+p+p+p-p+p+p+p+p+p+p+p+p+p-p+p+p+p+p+p+pREDD1RabJAKTCL1PHLPPCREBULKPFKHif2aHif3aRps6kb2Eif4ebp1Eif4bRps6kb1Rps6Eif4eEif4e2Eif4e1bPik3c2bPik3c2aPik3c2gPI3K (class II)Ins1Ins1InsrIrs1Irs4Irs3Irs2


Description

Cell-matrix adhesions play essential roles in important biological processes including cell motility, cell proliferation, cell differentiation, regulation of gene expression and cell survival. At the cell-extracellular matrix contact points, specialized structures are formed and termed focal adhesions, where bundles of actin filaments are anchored to transmembrane receptors of the integrin family through a multi-molecular complex of junctional plaque proteins. Some of the constituents of focal adhesions participate in the structural link between membrane receptors and the actin cytoskeleton, while others are signalling molecules, including different protein kinases and phosphatases, their substrates, and various adapter proteins. Integrin signaling is dependent upon the non-receptor tyrosine kinase activities of the FAK and src proteins as well as the adaptor protein functions of FAK, src and Shc to initiate downstream signaling events. These signalling events culminate in reorganization of the actin cytoskeleton; a prerequisite for changes in cell shape and motility, and gene expression. Similar morphological alterations and modulation of gene expression are initiated by the binding of growth factors to their respective receptors, emphasizing the considerable crosstalk between adhesion- and growth factor-mediated signalling.

Source: KEGG http://www.genome.jp/kegg-bin/show_pathway?org_name=mmu&mapno=04151 http://www.genome.jp/kegg-bin/show_pathway?org_name=mmu&mapno=04150

http://www.genome.jp/kegg-bin/show_pathway?org_name=mmu&mapno=04152

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Bibliography

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  1. Vanhaesebroeck B, Alessi DR; ''The PI3K-PDK1 connection: more than just a road to PKB.''; Biochem J, 2000 PubMed Europe PMC Scholia
  2. Turner CE; ''Paxillin and focal adhesion signalling.''; Nat Cell Biol, 2000 PubMed Europe PMC Scholia
  3. Lee JW, Juliano R; ''Mitogenic signal transduction by integrin- and growth factor receptor-mediated pathways.''; Mol Cells, 2004 PubMed Europe PMC Scholia
  4. Berman AE, Kozlova NI, Morozevich GE; ''Integrins: structure and signaling.''; Biochemistry (Mosc), 2003 PubMed Europe PMC Scholia
  5. Schlaepfer DD, Mitra SK; ''Multiple connections link FAK to cell motility and invasion.''; Curr Opin Genet Dev, 2004 PubMed Europe PMC Scholia
  6. Hlobilková A, Knillová J, Bártek J, Lukás J, Kolár Z; ''The mechanism of action of the tumour suppressor gene PTEN.''; Biomed Pap Med Fac Univ Palacky Olomouc Czech Repub, 2003 PubMed Europe PMC Scholia
  7. Danen EH, Yamada KM; ''Fibronectin, integrins, and growth control.''; J Cell Physiol, 2001 PubMed Europe PMC Scholia
  8. Comoglio PM, Boccaccio C, Trusolino L; ''Interactions between growth factor receptors and adhesion molecules: breaking the rules.''; Curr Opin Cell Biol, 2003 PubMed Europe PMC Scholia
  9. Burridge K, Wennerberg K; ''Rho and Rac take center stage.''; Cell, 2004 PubMed Europe PMC Scholia
  10. Parsons JT; ''Focal adhesion kinase: the first ten years.''; J Cell Sci, 2003 PubMed Europe PMC Scholia
  11. Oloumi A, McPhee T, Dedhar S; ''Regulation of E-cadherin expression and beta-catenin/Tcf transcriptional activity by the integrin-linked kinase.''; Biochim Biophys Acta, 2004 PubMed Europe PMC Scholia
  12. Guo W, Giancotti FG; ''Integrin signalling during tumour progression.''; Nat Rev Mol Cell Biol, 2004 PubMed Europe PMC Scholia
  13. Nicholson KM, Anderson NG; ''The protein kinase B/Akt signalling pathway in human malignancy.''; Cell Signal, 2002 PubMed Europe PMC Scholia
  14. Stupack DG, Cheresh DA; ''Get a ligand, get a life: integrins, signaling and cell survival.''; J Cell Sci, 2002 PubMed Europe PMC Scholia
  15. Mitra SK, Hanson DA, Schlaepfer DD; ''Focal adhesion kinase: in command and control of cell motility.''; Nat Rev Mol Cell Biol, 2005 PubMed Europe PMC Scholia
  16. Petit V, Thiery JP; ''Focal adhesions: structure and dynamics.''; Biol Cell, 2000 PubMed Europe PMC Scholia
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History

View all...
CompareRevisionActionTimeUserComment
128757view12:59, 21 February 2024EweitzUpgrade disease node, standardize case
116712view09:46, 11 May 2021EweitzModified title
94308view11:43, 1 September 2017Marvin M2Changed membrane lines into graphical lines
94215view21:49, 25 August 2017DeSlAdded IDs for insulin and NO
89989view19:07, 6 October 2016Mkutmonfixed unconnected lines
89334view10:20, 4 September 2016ZganReverted to version '10:08, 4 September 2016' by Zgan
89333view10:20, 4 September 2016ZganAdd the link of NO, insulin to PI3K
89332view10:08, 4 September 2016ZganPeriodical save, work in progress
82880view12:16, 11 November 2015JmeliusCorrect outdated id
80939view23:54, 30 June 2015Zgancorrection
80222view17:22, 26 May 2015Zgancuration of insulin signaling
79834view09:44, 17 April 2015EgonwReplaced a gene name with its Entrez Gene identifier.
79327view11:17, 21 March 2015EgonwRemoved a linkout the Entrez Gene that doesn't exist.
79326view11:02, 21 March 2015EgonwFixed the character encoding of a few authors in the reference list.
79303view19:12, 20 March 2015ZganModified title
78867view19:15, 9 February 2015Khanspersremoved old genmapp comments
78817view05:17, 1 February 2015Zganrelation added
78816view05:15, 1 February 2015ZganPI3K class II integrated
78815view05:12, 1 February 2015ZganSpecify description
78814view05:10, 1 February 2015ZganModified title
78421view10:26, 7 January 2015MaintBotadded missing graphIds
77383view21:44, 2 September 2014Zgandetails added
77382view21:36, 2 September 2014ZganOntology Term : 'phosphatidylinositol 3-kinase signaling pathway' added !
77381view21:35, 2 September 2014ZganOntology Term : 'signaling pathway' added !
77360view00:59, 28 August 2014Zgancorrection
77349view19:08, 26 August 2014KhanspersOntology Term : 'mTOR signaling pathway' added !
77313view22:15, 14 August 2014ZganNew pathway

External references

DataNodes

View all...
NameTypeDatabase referenceComment
AcacaGeneProduct107476 (Entrez Gene)
Akt1GeneProduct11651 (Entrez Gene)
Akt1s1GeneProduct67605 (Entrez Gene) SOS1; son of sevenless homolog 1 (Drosophila)
Akt2GeneProduct11652 (Entrez Gene)
Akt3GeneProduct23797 (Entrez Gene)
Angpt1GeneProduct11600 (Entrez Gene)
Angpt2GeneProduct11601 (Entrez Gene)
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Atf2GeneProduct11909 (Entrez Gene)
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Atf6bGeneProduct12915 (Entrez Gene)
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Cab39GeneProduct12283 (Entrez Gene)
Cab39lGeneProduct69008 (Entrez Gene)
Casp9GeneProduct12371 (Entrez Gene) SOS1; son of sevenless homolog 1 (Drosophila)
Cdc37GeneProduct12539 (Entrez Gene)
Cdkn1aGeneProduct12575 (Entrez Gene) SOS1; son of sevenless homolog 1 (Drosophila)
Cdkn1bGeneProduct12576 (Entrez Gene) SOS1; son of sevenless homolog 1 (Drosophila)
ChadGeneProduct12643 (Entrez Gene)
Chrm1GeneProduct12669 (Entrez Gene)
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Foxo3GeneProduct56484 (Entrez Gene) SOS1; son of sevenless homolog 1 (Drosophila)
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Gm15776GeneProduct100043507 (Entrez Gene)
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Gsk3bGeneProduct56637 (Entrez Gene) SOS1; son of sevenless homolog 1 (Drosophila)
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Gys2GeneProduct232493 (Entrez Gene)
HgfGeneProduct15234 (Entrez Gene)
Hif1a GeneProduct15251 (Entrez Gene)
Hif2a GeneProduct13819 (Entrez Gene)
Hif3a GeneProduct53417 (Entrez Gene)
HmgcrGeneProduct15375 (Entrez Gene)
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Hsp90aa1GeneProduct15519 (Entrez Gene)
Hsp90ab1GeneProduct15516 (Entrez Gene)
Hsp90b1GeneProduct22027 (Entrez Gene)
IbspGeneProduct15891 (Entrez Gene)
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IfnabGeneProduct15974 (Entrez Gene)
Ifnar1GeneProduct15975 (Entrez Gene)
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Ifnb1GeneProduct15977 (Entrez Gene)
Igf1rGeneProduct16001 (Entrez Gene)
IkbkbGeneProduct16150 (Entrez Gene) SOS1; son of sevenless homolog 1 (Drosophila)
IkbkgGeneProduct16151 (Entrez Gene) SOS1; son of sevenless homolog 1 (Drosophila)
Il2GeneProduct16183 (Entrez Gene)
Il2raGeneProduct16184 (Entrez Gene)
Il2rbGeneProduct16185 (Entrez Gene)
Il2rgGeneProduct16186 (Entrez Gene)
Il3raGeneProduct16188 (Entrez Gene)
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Ins1GeneProduct16333 (Entrez Gene)
Ins1GeneProduct16334 (Entrez Gene)
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Irs1GeneProduct16367 (Entrez Gene)
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Itga10GeneProduct213119 (Entrez Gene)
Itga11GeneProduct319480 (Entrez Gene)
Itga2GeneProduct16398 (Entrez Gene)
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Itga3GeneProduct16400 (Entrez Gene)
Itga4GeneProduct16401 (Entrez Gene)
Itga5GeneProduct16402 (Entrez Gene)
Itga6GeneProduct16403 (Entrez Gene)
Itga7GeneProduct16404 (Entrez Gene)
Itga8GeneProduct241226 (Entrez Gene)
Itga9GeneProduct104099 (Entrez Gene)
ItgadGeneProduct381924 (Entrez Gene)
ItgaeGeneProduct16407 (Entrez Gene)
ItgalGeneProduct16408 (Entrez Gene)
ItgamGeneProduct16409 (Entrez Gene)
ItgavGeneProductMGI:96608 (MGI)
ItgaxGeneProduct16411 (Entrez Gene)
Itgb1GeneProduct16412 (Entrez Gene)
Itgb2GeneProduct16414 (Entrez Gene)
Itgb3GeneProduct16416 (Entrez Gene)
Itgb4GeneProduct192897 (Entrez Gene)
Itgb5GeneProduct16419 (Entrez Gene)
Itgb6GeneProduct16420 (Entrez Gene)
Itgb7GeneProduct16421 (Entrez Gene)
Itgb8GeneProduct320910 (Entrez Gene)
Jak1GeneProduct16451 (Entrez Gene) CAV1; caveolin 1 caveolae protein 22kD
Jak2GeneProduct16452 (Entrez Gene) CAV2; caveolin 2
Jak3GeneProduct16453 (Entrez Gene) CAV3; caveolin 3
KdrGeneProduct16542 (Entrez Gene)
Kik1b4GeneProduct18084 (Entrez Gene)
KitGeneProduct16590 (Entrez Gene)
KitlGeneProduct17311 (Entrez Gene)
KrasGeneProduct16653 (Entrez Gene) SOS1; son of sevenless homolog 1 (Drosophila)
LOC235580GeneProduct
Lama1GeneProduct16772 (Entrez Gene)
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Lama3GeneProductENSMUSG00000024421 (Ensembl)
Lama4GeneProduct16775 (Entrez Gene)
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Lamb1-1GeneProduct16777 (Entrez Gene)
Lamb2GeneProduct16779 (Entrez Gene)
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Lamc1GeneProduct226519 (Entrez Gene)
Lamc2GeneProduct16782 (Entrez Gene)
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Lpar3GeneProduct65086 (Entrez Gene)
Lpar4GeneProduct78134 (Entrez Gene)
Lpar5GeneProduct381810 (Entrez Gene)
Lpar6GeneProduct67168 (Entrez Gene)
Map2k1GeneProduct26395 (Entrez Gene) SOS1; son of sevenless homolog 1 (Drosophila)
Mapk1GeneProduct26413 (Entrez Gene) SOS1; son of sevenless homolog 1 (Drosophila)
Mapk2k2GeneProduct26396 (Entrez Gene) SOS1; son of sevenless homolog 1 (Drosophila)
Mapk3GeneProduct26417 (Entrez Gene) SOS1; son of sevenless homolog 1 (Drosophila)
Mdm2GeneProduct17246 (Entrez Gene) SOS1; son of sevenless homolog 1 (Drosophila)
MetGeneProduct17295 (Entrez Gene)
Mlst8GeneProduct56716 (Entrez Gene)
Mtcp1GeneProduct17763 (Entrez Gene)
MtorGeneProduct56717 (Entrez Gene)
NgfGeneProduct18049 (Entrez Gene)
NgfrGeneProduct18053 (Entrez Gene)
Nos1GeneProduct18125 (Entrez Gene) SOS1; son of sevenless homolog 1 (Drosophila)
Nos2GeneProduct18126 (Entrez Gene) SOS1; son of sevenless homolog 1 (Drosophila)
Nos3GeneProduct18127 (Entrez Gene) SOS1; son of sevenless homolog 1 (Drosophila)
NrasGeneProduct18176 (Entrez Gene) SOS1; son of sevenless homolog 1 (Drosophila)
OsmGeneProduct18413 (Entrez Gene)
OsmrGeneProduct18414 (Entrez Gene)
PdgfaGeneProduct18590 (Entrez Gene)
PdgfbGeneProduct18591 (Entrez Gene)
PdgfcGeneProduct54635 (Entrez Gene)
PdgfdGeneProduct71785 (Entrez Gene)
PdgfraGeneProduct18595 (Entrez Gene)
PdgfrbGeneProduct18596 (Entrez Gene)
Pdk1GeneProduct18607 (Entrez Gene)
PeloGeneProduct105083 (Entrez Gene)
Pfkfb1GeneProduct18639 (Entrez Gene)
Pfkfb2GeneProduct18640 (Entrez Gene)
Pfkfb3GeneProduct170768 (Entrez Gene)
Pfkfb4GeneProduct270198 (Entrez Gene)
PgfGeneProduct18654 (Entrez Gene)
Phllp1GeneProduct98432 (Entrez Gene)
Phlpp2GeneProduct244650 (Entrez Gene)
Pik3c2aGeneProduct18704 (Entrez Gene)
Pik3c2bGeneProduct240752 (Entrez Gene)
Pik3c2gGeneProduct18705 (Entrez Gene)
Pik3caGeneProduct18706 (Entrez Gene)
Pik3cbGeneProduct74769 (Entrez Gene)
Pik3cdGeneProduct18707 (Entrez Gene)
Pik3cgGeneProduct30955 (Entrez Gene)
Pik3ip1GeneProduct216505 (Entrez Gene)
Pik3r1GeneProduct18708 (Entrez Gene)
Pik3r2GeneProduct18709 (Entrez Gene)
Pik3r4GeneProduct75669 (Entrez Gene)
Pik3r5GeneProduct320207 (Entrez Gene)
Ppargc1aGeneProduct19017 (Entrez Gene)
Ppp2caGeneProduct19052 (Entrez Gene)
Ppp2cbGeneProduct19053 (Entrez Gene)
Ppp2r1aGeneProduct51792 (Entrez Gene)
Ppp2r1bGeneProduct73699 (Entrez Gene)
Ppp2r2bGeneProduct72930 (Entrez Gene)
Ppp2r2cGeneProduct269643 (Entrez Gene)
Ppp2r2dGeneProduct52432 (Entrez Gene)
Ppp2r3aGeneProduct235542 (Entrez Gene)
Ppp2r3cGeneProduct59032 (Entrez Gene)
Ppp2r3dGeneProduct19054 (Entrez Gene)
Ppp2r5bGeneProduct225849 (Entrez Gene)
Ppp2r5cGeneProduct26931 (Entrez Gene)
Ppp2r5dGeneProduct21770 (Entrez Gene)
Ppp2r5eGeneProduct26932 (Entrez Gene)
PrkaaGeneProduct105787 (Entrez Gene)
Prkaa2GeneProduct108079 (Entrez Gene)
PrlGeneProduct19109 (Entrez Gene)
PrlrGeneProduct19116 (Entrez Gene)
PtenGeneProduct19211 (Entrez Gene)
Ptk2GeneProduct14083 (Entrez Gene) DOCK1; dedicator of cyto-kinesis
Rab10GeneProduct19325 (Entrez Gene)
Rab11bGeneProduct19326 (Entrez Gene)
Rab14GeneProduct68365 (Entrez Gene)
Rab2aGeneProduct59021 (Entrez Gene)
Rab8aGeneProduct17274 (Entrez Gene)
Raf1GeneProduct110157 (Entrez Gene) SOS1; son of sevenless homolog 1 (Drosophila)
RelnGeneProduct19699 (Entrez Gene)
RhebGeneProduct19744 (Entrez Gene)
Rps6GeneProduct20104 (Entrez Gene)
Rps6kb1 GeneProduct72508 (Entrez Gene)
Rps6kb2 GeneProduct58988 (Entrez Gene)
RptorGeneProduct74370 (Entrez Gene)
Slc2a1GeneProduct20525 (Entrez Gene)
Slc2a2GeneProduct20526 (Entrez Gene)
Slc2a3GeneProduct20527 (Entrez Gene)
Slc2a4GeneProduct20528 (Entrez Gene)
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Spp1GeneProduct20750 (Entrez Gene)
Srebf1GeneProduct20787 (Entrez Gene)
Stk11GeneProduct20869 (Entrez Gene)
StradaGeneProduct72149 (Entrez Gene)
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Tcl1GeneProduct21432 (Entrez Gene)
Tcl1b1GeneProduct27379 (Entrez Gene)
Tcl1b4GeneProduct27380 (Entrez Gene)
TekGeneProduct21687 (Entrez Gene)
Thbs1GeneProduct21825 (Entrez Gene)
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Thbs3GeneProduct21827 (Entrez Gene)
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TncGeneProduct21923 (Entrez Gene)
TnnGeneProduct329278 (Entrez Gene)
TnrGeneProduct21960 (Entrez Gene)
TnxbGeneProduct81877 (Entrez Gene)
Tsc1GeneProduct64930 (Entrez Gene)
Tsc2GeneProduct22084 (Entrez Gene)
Ulk1GeneProduct22241 (Entrez Gene)
VegfaGeneProduct22339 (Entrez Gene)
VegfbGeneProduct22340 (Entrez Gene)
VegfcGeneProduct22341 (Entrez Gene)
VtnGeneProduct22370 (Entrez Gene)
VwfGeneProduct22371 (Entrez Gene)
ppp2r5aGeneProduct226849 (Entrez Gene)

Annotated Interactions

No annotated interactions

Retrieved from "https://classic.wikipathways.org/index.php/Pathway:WP2841"
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