Focal adhesion - Homo sapiens (human)

Curator(s): Joe Strothman

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.    
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Focal adhesion - Homo sapiens (human) cluster_ECM ECM cluster_node39 !who3 cluster_node40 !who cluster_Membrane Membrane cluster_node41 !who2 cluster_node42 !gf cluster_node43 !pip3 cluster_C3G C3G cluster_node44 Cell proliferation cluster_node45 !wnt cluster_node46 !map cluster_node47 Cell motility cluster_node48 Cell survival node1 4 node2 1 ITGA node2->ITGA ITGB node2->ITGB node3 19 node4 13 node5 2 v-src sarcoma (Schmidt-Ruppin A-2) viral oncogene homolog (avian) SRC SRC->node5 SRC RhoGAP SRC->RhoGAP +p FAK SRC->FAK +p ras homolog gene family,member A RHOA RhoGAP->RHOA FAK->SRC +p RhoGEF FAK->RhoGEF +p Shc FAK->Shc +p Calpain FAK->Calpain PI3K FAK->PI3K pl30Cas FAK->pl30Cas +p growth factor receptor-bound protein 2 GRB2 FAK->GRB2 Paxillin FAK->Paxillin +p node6 5 RhoGEF->RHOA Shc->GRB2 node7 1 Calpain->node7 Calpain Talin Calpain->Talin PIP5K RHOA->PIP5K ROCK RHOA->ROCK mDia1 RHOA->mDia1 PIP2 PIP5K->PIP2 Actin PIP2->Actin Vinculin PIP2->Vinculin MLC ROCK->MLC +p MLCP ROCK->MLCP +p node10 4 node10->Actin node11 2 phosphatase and tensin homolog PTEN PTEN->FAK -p PTEN->node11 PTEN PIP3 PTEN->PIP3 -p node12 3 node13 12 PI3K->node13 PI3K PI3K->PIP3 v-crk sarcoma virus CT10 oncogene homolog (avian) CRK pl30Cas->CRK dedicator of cytokinesis 1 DOCK1 CRK->DOCK1 CRK->Paxillin GRF2 CRK->GRF2 Sos GRB2->Sos node14 2 Sos->node14 Sos node15 Ha-Ras Sos->node15 node15->PI3K mDia1->Actin MLC->Actin Filopodia Lamellipodia formation Actin->Filopodia Lamellipodia formation node35 Stress fiber / FA formation Actin->node35 MLCK MLCK->MLC +p MLCP->MLC -p pyruvate dehydrogenase kinase,isozyme 1 PDK1 node17 Akt/PKB PDK1->node17 +p node16 17 node17->node16 Akt/PKB node19 GSK-3beta node17->node19 +p Apoptosis node17->Apoptosis node18 5 node19->node18 GSK-3beta node21 B-Catenin node19->node21 +p node20 5 DNA CycD DNA->CycD Cell survival Apoptosis->Cell survival Vav Rac Vav->Rac Rac->Actin +p PAK Rac->PAK JNK Rac->JNK +p cell division cycle 42 (GTP binding protein,25kDa) CDC42 CDC42->Actin CDC42->Rac CDC42->PAK PAK->MLCK +p node23 Raf-1 PAK->node23 +p MEK1 PAK->MEK1 +p FA turnover PAK->FA turnover node22 2 node23->node22 Raf-1 BCL2-associated agonist of cell death BAD node23->BAD +p node24 B-Raf node24->MEK1 +p Rap1 Rap1->node24 node25 2 MEK1->node25 MEK1 MEK1->BAD +p node30 ERK1/2 MEK1->node30 +p node26 11 JNK->node26 JNK node28 c-Jun JNK->node28 +p node27 1 node28->DNA node28->node27 c-Jun node29 15 ELK1,member of ETS oncogene family ELK1 ELK1->DNA DNA 2 ELK1->DNA 2 node31 2 BAD->node31 BAD node32 21 node33 Bcl-2 node33->node32 Bcl-2 node33->Cell survival cIAPs DNA 2->cIAPs node34 10 node36 2 DOCK1->Rac node9 3 ITGA->node9 ITGB->SRC ITGB->FAK ITGB->node9 Caveolin ITGB->Caveolin PKC ITGB->PKC node8 2 Actinin node8->Actinin Filamin node8->Filamin node8->Paxillin node8->Talin Actinin->Vinculin Zyxin Actinin->Zyxin Paxillin->Actin integrin-linked kinase ILK Paxillin->ILK Talin->Vinculin node9->node8 Vinculin->node10 Zyxin->node10 node21->node20 B-Catenin node21->DNA GRF2->Rap1 FYN oncogene related to SRC,FGR,YES FYN Caveolin->FYN FYN->Shc +p CycD->node34 CycD cIAPs->node36 cIAPs ECM 1 ECM 1->node2 ECM 2 ECM 2->node2 ECM 3 ECM 3->node1 ECM 3 ECM 3->node2 node30->node29 ERK1/2 node30->ELK1 +p node30->node33 +p GF GF->node3 GF RTK GF->RTK RTK->node4 RTK RTK->FAK RTK->Shc RTK->PI3K ILK->node17 +p Parvin ILK->Parvin Parvin->node10 PKC->FAK +p PKC->node6 PKC PIP3->node12 PIP3 PIP3->PDK1 PIP3->node17 PIP3->Vav PIP3->ILK vasodilator-stimulated phosphoprotein VASP VASP->node10 Phosphatidylinositol SS Wnt signaling pathway MAPK Signaling Pathway Cell cycle Regulation of actin cytoskeleton Actin polymerization node37 Cytokine -cytokine receptor interaction - Homo sapiens node38 ECM-receptor interaction print "