Focal adhesion: PI3K-Akt-mTOR signaling pathway (WP2841)

Mus musculus

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

Authors

Zhuohui Gan , Kristina Hanspers , Egon Willighagen , Jonathan Mélius , Martina Summer-Kutmon , Denise Slenter , Marvin Martens , and Eric Weitz

Activity

last edited

Discuss this pathway

Check for ongoing discussions or start your own.

Cited In

Are you planning to include this pathway in your next publication? See How to Cite and add a link here to your paper once it's online.

Organisms

Mus musculus

Communities

Annotations

Pathway Ontology

signaling pathway cell adhesion signaling pathway mTOR signaling pathway phosphatidylinositol 3-kinase signaling pathway

Participants

Label Type Compact URI Comment
NO Metabolite chebi:29120
Insulin Metabolite chebi:5931
Col4a1 GeneProduct ncbigene:12826
Tsc2 GeneProduct ncbigene:22084
Col5a3 GeneProduct ncbigene:53867
Thbs4 GeneProduct ncbigene:21828
Prlr GeneProduct ncbigene:19116
Sos1 GeneProduct ncbigene:20662 SOS1; son of sevenless homolog 1 (Drosophila)
Col5a1 GeneProduct ncbigene:12831
Itgb6 GeneProduct ncbigene:16420
Pelo GeneProduct ncbigene:105083
Jak3 GeneProduct ncbigene:16453 CAV3; caveolin 3
Il2rg GeneProduct ncbigene:16186
Itga11 GeneProduct ncbigene:319480
Col11a2 GeneProduct ncbigene:12815
Lamb3 GeneProduct ncbigene:16780
Grb2 GeneProduct ncbigene:14784 GRB2; growth factor receptor-bound protein 2
Tnn GeneProduct ncbigene:329278
Stk11 GeneProduct ncbigene:20869
Gh GeneProduct ncbigene:14599
Il3ra GeneProduct ncbigene:16188
Epor GeneProduct ncbigene:13857
Itga7 GeneProduct ncbigene:16404
Itgam GeneProduct ncbigene:16409
Col1a2 GeneProduct ncbigene:12843
Pik3ip1 GeneProduct ncbigene:216505
Ibsp GeneProduct ncbigene:15891
Col5a2 GeneProduct ncbigene:12832
Osmr GeneProduct ncbigene:18414
Col4a6 GeneProduct ncbigene:94216
Thbs3 GeneProduct ncbigene:21827
Itga2 GeneProduct ncbigene:16398
Lama2 GeneProduct ncbigene:16773
Col2a1 GeneProduct ncbigene:12824
Col4a4 GeneProduct ncbigene:12829
Csf3 GeneProduct ncbigene:12985
Itgb4 GeneProduct ncbigene:192897
Itga5 GeneProduct ncbigene:16402
Lama4 GeneProduct ncbigene:16775
Itgb8 GeneProduct ncbigene:320910
Itgad GeneProduct ncbigene:381924
Itgb3 GeneProduct ncbigene:16416
Lama5 GeneProduct ncbigene:16776
Ptk2 GeneProduct ncbigene:14083 DOCK1; dedicator of cyto-kinesis
Chad GeneProduct ncbigene:12643
Itga10 GeneProduct ensembl:ENSMUSG00000090210
Tnxb GeneProduct ncbigene:81877
Itga3 GeneProduct ncbigene:16400
Col1a1 GeneProduct ncbigene:12842
Itga6 GeneProduct ncbigene:16403
Epo GeneProduct ncbigene:13856
Itgav GeneProduct mgi:MGI:96608
Lama1 GeneProduct ncbigene:16772
Vwf GeneProduct ncbigene:22371
Col3a1 GeneProduct ncbigene:12825
Akt3 GeneProduct ncbigene:23797
Itgax GeneProduct ncbigene:16411
Itgb2 GeneProduct ncbigene:16414
Il4ra GeneProduct ncbigene:16190
Itga2b GeneProduct ncbigene:16399
Csf3r GeneProduct ncbigene:12986
Ifnar2 GeneProduct ncbigene:15976
Lamc3 GeneProduct ncbigene:23928
Il7r GeneProduct ncbigene:16197
Thbs2 GeneProduct ncbigene:21826
Itgb7 GeneProduct ncbigene:16421
Ifna2 GeneProduct ncbigene:15965
Spp1 GeneProduct ncbigene:20750
Fn1 GeneProduct ncbigene:14268
Ddit4 GeneProduct ncbigene:74747
Col11a1 GeneProduct ncbigene:12814
Itga4 GeneProduct ncbigene:16401
Jak2 GeneProduct ncbigene:16452 CAV2; caveolin 2
Jak1 GeneProduct ncbigene:16451 CAV1; caveolin 1 caveolae protein 22kD
Vtn GeneProduct ncbigene:22370
Ifna1 GeneProduct ncbigene:15962
Ifna11 GeneProduct ncbigene:15964
Akt1 GeneProduct ncbigene:11651
Pik3cb GeneProduct ncbigene:74769
Pik3cd GeneProduct ncbigene:18707
Ghr GeneProduct ncbigene:14600
Il6ra GeneProduct ncbigene:16194
Comp GeneProduct ncbigene:12845
Lamc1 GeneProduct ncbigene:226519
Lamb2 GeneProduct ncbigene:16779
Il2rb GeneProduct ncbigene:16185
Pik3ca GeneProduct ncbigene:18706
Lama3 GeneProduct ensembl:ENSMUSG00000024421
Il2ra GeneProduct ncbigene:16184
Pten GeneProduct ncbigene:19211
Lamb1-1 GeneProduct ncbigene:16777
Reln GeneProduct ncbigene:19699
Pik3r4 GeneProduct ncbigene:75669
Col4a2 GeneProduct ncbigene:12827
Tsc1 GeneProduct ncbigene:64930
Itgb1 GeneProduct ncbigene:16412
Itga8 GeneProduct ncbigene:241226
Itgae GeneProduct ncbigene:16407
Itga9 GeneProduct ncbigene:104099
Col6a2 GeneProduct ncbigene:12834
Itgb5 GeneProduct ncbigene:16419
Thbs1 GeneProduct ncbigene:21825
Itgal GeneProduct ncbigene:16408
Akt2 GeneProduct ncbigene:11652
Pik3r1 GeneProduct ncbigene:18708
Pik3r2 GeneProduct ncbigene:18709
Lamc2 GeneProduct ncbigene:16782
Tnc GeneProduct ncbigene:21923
Ifnar1 GeneProduct ncbigene:15975
Tnr GeneProduct ncbigene:21960
Pik3r5 GeneProduct ncbigene:320207
Efna1 GeneProduct ncbigene:13636
Fgf GeneProduct ncbigene:14164
Fgf11 GeneProduct ncbigene:14166
Fgf10 GeneProduct ncbigene:14165
Efna2 GeneProduct ncbigene:13637
Egf GeneProduct ncbigene:13645
Fgf12 GeneProduct ncbigene:14167
Csf1 GeneProduct ncbigene:12977
Angpt4 GeneProduct ncbigene:11602
Angpt2 GeneProduct ncbigene:11601
Angpt1 GeneProduct ncbigene:11600
Vegfa GeneProduct ncbigene:22339
Efna3 GeneProduct ncbigene:13638
Efna4 GeneProduct ncbigene:13639
Efna5 GeneProduct ncbigene:13640
Fgf14 GeneProduct ncbigene:14169
Fgf13 GeneProduct ncbigene:14168
Fgf15 GeneProduct ncbigene:14170
Fgf17 GeneProduct ncbigene:14171
Fgf18 GeneProduct ncbigene:14172
Fgf2 GeneProduct ncbigene:14173
Fgf3 GeneProduct ncbigene:14174
Fgf4 GeneProduct ncbigene:14175
Fgf6 GeneProduct ncbigene:14177
Fgf7 GeneProduct ncbigene:14178
Fgf8 GeneProduct ncbigene:14179
Fgf9 GeneProduct ncbigene:14180
Figf GeneProduct ncbigene:14205
Hgf GeneProduct ncbigene:15234
Ifg1 GeneProduct ncbigene:16000
Ins1 GeneProduct ncbigene:16333
Ins2 GeneProduct ncbigene:16334
Kitl GeneProduct ncbigene:17311
Kik1b4 GeneProduct ncbigene:18084
Kik1b4 GeneProduct ncbigene:18084
Vegfc GeneProduct ncbigene:22341
Vegfb GeneProduct ncbigene:22340
Pdgfb GeneProduct ncbigene:18591
Pgf GeneProduct ncbigene:18654
Pdgfa GeneProduct ncbigene:18590
Ngf GeneProduct ncbigene:18049
Pdgfc GeneProduct ncbigene:54635
Fgf21 GeneProduct ncbigene:56636
Fgf23 GeneProduct ncbigene:54654
Fgf22 GeneProduct ncbigene:67112
Pdgfd GeneProduct ncbigene:71785
Fgf20 GeneProduct ncbigene:80857
Fgf16 GeneProduct ncbigene:80903
Fgfr2 GeneProduct ncbigene:14183
Kdr GeneProduct ncbigene:16542
Insr GeneProduct ncbigene:16337
Fgfr3 GeneProduct ncbigene:14184
Igf1r GeneProduct ncbigene:16001
Kit GeneProduct ncbigene:16590
Fgfr1 GeneProduct ncbigene:14182
Epha2 GeneProduct ncbigene:13836
Egfr GeneProduct ncbigene:13649
Csf1r GeneProduct ncbigene:12978
Fgfr4 GeneProduct ncbigene:14186
Flt1 GeneProduct ncbigene:14254
Flt4 GeneProduct ncbigene:14257
Ngfr GeneProduct ncbigene:18053
Met GeneProduct ncbigene:17295
Pdgfra GeneProduct ncbigene:18595
Pdgfrb GeneProduct ncbigene:18596
Tek GeneProduct ncbigene:21687
Akt1s1 GeneProduct ncbigene:67605 SOS1; son of sevenless homolog 1 (Drosophila)
Ifna4 GeneProduct ncbigene:15967
Ifna5 GeneProduct ncbigene:15968
Ifna6 GeneProduct ncbigene:15969
Ifna7 GeneProduct ncbigene:15970
Ifna9 GeneProduct ncbigene:15972
Ifnab GeneProduct ncbigene:15974
Ifnb1 GeneProduct ncbigene:15977
Il2 GeneProduct ncbigene:16183
Osm GeneProduct ncbigene:18413
Prl GeneProduct ncbigene:19109
Ifna13 GeneProduct ncbigene:230396
Gm12597 GeneProduct ncbigene:241517
Ifna12 GeneProduct ncbigene:241519
Ifna14 GeneProduct ncbigene:404549
Chrm1 GeneProduct ncbigene:12669
Lpar1 GeneProduct ncbigene:14745
F2r GeneProduct ncbigene:14062
Chrm2 GeneProduct ncbigene:243764
Lpar5 GeneProduct ncbigene:381810
Lpar2 GeneProduct ncbigene:53978
Lpar3 GeneProduct ncbigene:65086
Lpar6 GeneProduct ncbigene:67168
Lpar4 GeneProduct ncbigene:78134
Gm15776 GeneProduct ncbigene:100043507
Gnb2 GeneProduct ncbigene:14693
Gnb1 GeneProduct ncbigene:14688
Gm5741 GeneProduct ncbigene:100503710
Gnb4 GeneProduct ncbigene:14696
Gngt1 GeneProduct ncbigene:14699
Gng10 GeneProduct ncbigene:14700
Gng12 GeneProduct ncbigene:14701
Gnb3 GeneProduct ncbigene:14695
Gng2 GeneProduct ncbigene:14702
Gng3 GeneProduct ncbigene:14704
Gng4 GeneProduct ncbigene:14706
Gng5 GeneProduct ncbigene:14707
Gng7 GeneProduct ncbigene:14708
Gng8 GeneProduct ncbigene:14709
Gngt2 GeneProduct ncbigene:14710
Gng13 GeneProduct ncbigene:64337
Gng11 GeneProduct ncbigene:66066
Pik3cg GeneProduct ncbigene:30955
Nras GeneProduct ncbigene:18176 SOS1; son of sevenless homolog 1 (Drosophila)
Kras GeneProduct ncbigene:16653 SOS1; son of sevenless homolog 1 (Drosophila)
Hras GeneProduct ncbigene:15461 SOS1; son of sevenless homolog 1 (Drosophila)
Strada GeneProduct ncbigene:72149
Cab39 GeneProduct ncbigene:12283
Cab39l GeneProduct ncbigene:69008
Prkaa GeneProduct ncbigene:105787
Prkaa2 GeneProduct ncbigene:108079
Mlst8 GeneProduct ncbigene:56716
Rheb GeneProduct ncbigene:19744
Mtor GeneProduct ncbigene:56717
Rptor GeneProduct ncbigene:74370
Hif1a GeneProduct ncbigene:15251
Ulk1 GeneProduct ncbigene:22241
Crtc2 GeneProduct ncbigene:74343
Cdc37 GeneProduct ncbigene:12539
Hsp90ab1 GeneProduct ncbigene:15516
Phllp1 GeneProduct ncbigene:98432
Tcl1 GeneProduct ncbigene:21432
Pdk1 GeneProduct ncbigene:18607
Gm2436 GeneProduct ncbigene:100039815
Ppp2cb GeneProduct ncbigene:19053
Ppp2ca GeneProduct ncbigene:19052
Gm2446 GeneProduct ncbigene:100039830
Ppp2r5d GeneProduct ncbigene:21770
Ppp2r5b GeneProduct ncbigene:225849
Ppp2r2b GeneProduct ncbigene:72930
Ppp2r1b GeneProduct ncbigene:73699
Ppp2r3d GeneProduct ncbigene:19054
Ppp2r3a GeneProduct ncbigene:235542
Ppp2r5c GeneProduct ncbigene:26931
Ppp2r5e GeneProduct ncbigene:26932
Ppp2r2c GeneProduct ncbigene:269643
Ppp2r1a GeneProduct ncbigene:51792
Ppp2r2d GeneProduct ncbigene:52432
ppp2r5a GeneProduct ncbigene:226849
Ppp2r3c GeneProduct ncbigene:59032
Hsp90aa1 GeneProduct ncbigene:15519
Hsp90b1 GeneProduct ncbigene:22027
Phlpp2 GeneProduct ncbigene:244650
Mtcp1 GeneProduct ncbigene:17763
Tcl1b1 GeneProduct ncbigene:27379
Tcl1b4 GeneProduct ncbigene:27380
Raf1 GeneProduct ncbigene:110157 SOS1; son of sevenless homolog 1 (Drosophila)
Mapk2k2 GeneProduct ncbigene:26396 SOS1; son of sevenless homolog 1 (Drosophila)
Map2k1 GeneProduct ncbigene:26395 SOS1; son of sevenless homolog 1 (Drosophila)
Mapk1 GeneProduct ncbigene:26413 SOS1; son of sevenless homolog 1 (Drosophila)
Mapk3 GeneProduct ncbigene:26417 SOS1; son of sevenless homolog 1 (Drosophila)
Gsk3b GeneProduct ncbigene:56637 SOS1; son of sevenless homolog 1 (Drosophila)
Foxo3 GeneProduct ncbigene:56484 SOS1; son of sevenless homolog 1 (Drosophila)
Foxo1 GeneProduct ncbigene:56458 SOS1; son of sevenless homolog 1 (Drosophila)
Ikbkb GeneProduct ncbigene:16150 SOS1; son of sevenless homolog 1 (Drosophila)
Bad GeneProduct ncbigene:12015 SOS1; son of sevenless homolog 1 (Drosophila)
Casp9 GeneProduct ncbigene:12371 SOS1; son of sevenless homolog 1 (Drosophila)
Mdm2 GeneProduct ncbigene:17246 SOS1; son of sevenless homolog 1 (Drosophila)
Ikbkg GeneProduct ncbigene:16151 SOS1; son of sevenless homolog 1 (Drosophila)
Cdkn1b GeneProduct ncbigene:12576 SOS1; son of sevenless homolog 1 (Drosophila)
Cdkn1a GeneProduct ncbigene:12575 SOS1; son of sevenless homolog 1 (Drosophila)
Atf2 GeneProduct ncbigene:11909
Creb3 GeneProduct ncbigene:12913
Creb1 GeneProduct ncbigene:12912
Atf4 GeneProduct ncbigene:11911
Creb3l2 GeneProduct ncbigene:208647
Creb3l3 GeneProduct ncbigene:208677
Atf6b GeneProduct ncbigene:12915
Creb3l1 GeneProduct ncbigene:26427
Creb3l4 GeneProduct ncbigene:78284
Creb5 GeneProduct ncbigene:231991
Nos3 GeneProduct ncbigene:18127 SOS1; son of sevenless homolog 1 (Drosophila)
Tbc1d1 GeneProduct ncbigene:57915
Rab8a GeneProduct ncbigene:17274
Rab2a GeneProduct ncbigene:59021
Rab10 GeneProduct ncbigene:19325
Rab11b GeneProduct ncbigene:19326
Rab14 GeneProduct ncbigene:68365
Slc2a4 GeneProduct ncbigene:20528
Slc2a1 GeneProduct ncbigene:20525
Slc2a3 GeneProduct ncbigene:20527
Slc2a2 GeneProduct ncbigene:20526
Ppargc1a GeneProduct ncbigene:19017
Gys1 GeneProduct ncbigene:14936
Gys2 GeneProduct ncbigene:232493
Pfkfb2 GeneProduct ncbigene:18640
Pfkfb1 GeneProduct ncbigene:18639
Pfkfb3 GeneProduct ncbigene:170768
Pfkfb4 GeneProduct ncbigene:270198
Lipe GeneProduct ncbigene:16890
Srebf1 GeneProduct ncbigene:20787
Hmgcr GeneProduct ncbigene:15375
Acaca GeneProduct ncbigene:107476
Elavl1 GeneProduct ncbigene:15568
Nos1 GeneProduct ncbigene:18125 SOS1; son of sevenless homolog 1 (Drosophila)
Nos2 GeneProduct ncbigene:18126 SOS1; son of sevenless homolog 1 (Drosophila)
Hif2a GeneProduct ncbigene:13819
Hif3a GeneProduct ncbigene:53417
Rps6kb2 GeneProduct ncbigene:58988
Eif4ebp1 GeneProduct ncbigene:13685
Eif4b GeneProduct ncbigene:75705
Rps6kb1 GeneProduct ncbigene:72508
Rps6 GeneProduct ncbigene:20104
Eif4e GeneProduct ncbigene:13684
Eif4e2 GeneProduct ncbigene:26987
Eif4e1b GeneProduct ncbigene:218268
Pik3c2b GeneProduct ncbigene:240752
Pik3c2a GeneProduct ncbigene:18704
Pik3c2g GeneProduct ncbigene:18705
Irs1 GeneProduct ncbigene:16367
Irs4 GeneProduct ncbigene:16370
Irs3 GeneProduct ncbigene:16369
Irs2 GeneProduct ncbigene:384783
Insr GeneProduct ncbigene:13677 GRB2; growth factor receptor-bound protein 2
Ins1 GeneProduct ncbigene:13633 GRB2; growth factor receptor-bound protein 2
Ins2 GeneProduct ncbigene:13634 GRB2; growth factor receptor-bound protein 2

References

  1. The PI3K-PDK1 connection: more than just a road to PKB. Vanhaesebroeck B, Alessi DR. Biochem J. 2000 Mar 15;346 Pt 3(Pt 3):561–76. PubMed Europe PMC Scholia
  2. Rho GTPases: signaling, migration, and invasion. Schmitz AA, Govek EE, Böttner B, Van Aelst L. Exp Cell Res. 2000 Nov 25;261(1):1–12. PubMed Europe PMC Scholia
  3. Paxillin and focal adhesion signalling. Turner CE. Nat Cell Biol. 2000 Dec;2(12):E231-6. PubMed Europe PMC Scholia
  4. Focal adhesions: structure and dynamics. Petit V, Thiery JP. Biol Cell. 2000 Oct;92(7):477–94. PubMed Europe PMC Scholia
  5. Fibronectin, integrins, and growth control. Danen EH, Yamada KM. J Cell Physiol. 2001 Oct;189(1):1–13. PubMed Europe PMC Scholia
  6. The protein kinase B/Akt signalling pathway in human malignancy. Nicholson KM, Anderson NG. Cell Signal. 2002 May;14(5):381–95. PubMed Europe PMC Scholia
  7. Get a ligand, get a life: integrins, signaling and cell survival. Stupack DG, Cheresh DA. J Cell Sci. 2002 Oct 1;115(Pt 19):3729–38. PubMed Europe PMC Scholia
  8. Focal adhesion kinase: the first ten years. Parsons JT. J Cell Sci. 2003 Apr 15;116(Pt 8):1409–16. PubMed Europe PMC Scholia
  9. Interactions between growth factor receptors and adhesion molecules: breaking the rules. Comoglio PM, Boccaccio C, Trusolino L. Curr Opin Cell Biol. 2003 Oct;15(5):565–71. PubMed Europe PMC Scholia
  10. Rho and Rac take center stage. Burridge K, Wennerberg K. Cell. 2004 Jan 23;116(2):167–79. PubMed Europe PMC Scholia
  11. Integrins: structure and signaling. Berman AE, Kozlova NI, Morozevich GE. Biochemistry (Mosc). 2003 Dec;68(12):1284–99. PubMed Europe PMC Scholia
  12. The mechanism of action of the tumour suppressor gene PTEN. Hlobilková A, Knillová J, Bártek J, Lukás J, Kolár Z. Biomed Pap Med Fac Univ Palacky Olomouc Czech Repub. 2003 Nov;147(1):19–25. PubMed Europe PMC Scholia
  13. Regulation of E-cadherin expression and beta-catenin/Tcf transcriptional activity by the integrin-linked kinase. Oloumi A, McPhee T, Dedhar S. Biochim Biophys Acta. 2004 Apr 1;1691(1):1–15. PubMed Europe PMC Scholia
  14. Multiple connections link FAK to cell motility and invasion. Schlaepfer DD, Mitra SK. Curr Opin Genet Dev. 2004 Feb;14(1):92–101. PubMed Europe PMC Scholia
  15. Mitogenic signal transduction by integrin- and growth factor receptor-mediated pathways. Lee JW, Juliano R. Mol Cells. 2004 Apr 30;17(2):188–202. PubMed Europe PMC Scholia
  16. Integrin signalling during tumour progression. Guo W, Giancotti FG. Nat Rev Mol Cell Biol. 2004 Oct;5(10):816–26. PubMed Europe PMC Scholia
  17. Focal adhesion kinase: in command and control of cell motility. Mitra SK, Hanson DA, Schlaepfer DD. Nat Rev Mol Cell Biol. 2005 Jan;6(1):56–68. PubMed Europe PMC Scholia