TGF-beta signaling pathway - Homo sapiens (human)

Curator(s): Peter D'Adamo

The transforming growth factor-beta (TGF-beta) family members, which include TGF-betas, activins and bone morphogenetic proteins (BMPs), are structurally related secreted cytokines found in species ranging from worms and insects to mammals. A wide spectrum of cellular functions such as proliferation, apoptosis, differentiation and migration are regulated by TGF-beta family members. TGF-beta family member binds to the Type II receptor and recruits Type I, whereby Type II receptor phosphorylates and activates Type I. The Type I receptor, in turn, phosphorylates receptor-activated Smads ( R-Smads: Smad1, Smad2, Smad3, Smad5, and Smad8). Once phosphorylated, R-Smads associate with the co-mediator Smad, Smad4, and the heteromeric complex then translocates into the nucleus. In the nucleus, Smad complexes activate specific genes through cooperative interactions with other DNA-binding and coactivator (or co-repressor) proteins.    
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TGF-beta signaling pathway - Homo sapiens (human) cluster_node33 CELL MEMBRANE Chordin BMP Chordin->BMP node1 4 BMP->node1 BMP node3 BMPRI BMPRII BMP->node3 node2 2 noggin NOG NOG->BMP NOG->node2 NOG DAN DAN->BMP Gremlin Gremlin->BMP node4 Smad1/5/8 node5 Smad1/5/8 Smad4 node4->node5 node6 1 node5->node6 DNA node6->DNA Id DNA->Id node7 2 Id->node7 Id DNA replication helicase 2 homolog (yeast) DNA2 Id->DNA2 Angiogenesis DNA2->Angiogenesis Osteoblast differentiation DNA2->Osteoblast differentiation Growth factors MAPK Signaling Pathway Growth factors->MAPK Signaling Pathway ERK MAPK Signaling Pathway->ERK node8 24 ERK->node6 ERK->node8 ERK node9 21 node10 IFNγ TNF node10->node9 IFNγ~TNF node12 Smad6/7 node10->node12 node11 2 node12->node4 node12->node11 Smad6/7 node14 Smad1/2 node12->node14 node15 Smurf1/2 node12->node15 node13 2 node14->node13 Smad1/2 Ubiquitin mediated proteolysis node15->Ubiquitin mediated proteolysis +u node16 TGFBRI TGFBRII node15->node16 node17 2 node18 Smad2/3 node18->node17 Smad2/3 node23 Smad2/3 Smad4 node18->node23 SARA SARA->node18 node19 12 TGFB TGFB->node19 TGFB TGFB->node16 Decorin Decorin->TGFB latent transforming growth factor beta binding protein 1 LTBP1 LTBP1->TGFB thrombospondin 1 THBS1 THBS1->LTBP1 Lefty Lefty->TGFB nodal homolog (mouse) NODAL Lefty->NODAL node21 NodalRI NodalRII NODAL->node21 follistatin FST Activin FST->Activin Activin->TGFB Activin->NODAL node20 ActivinRI ActivinRII Activin->node20 node22 2 node23->node22 Smad2/3~Smad4 DNA3 node23->DNA3 Transcription factors node23->Transcription factors node26 Co-activator node23->node26 node27 Co-repressor node23->node27 node28 p107 E2F4/5 DP1 node23->node28 node31 p300 SP1 node23->node31 paired-like homeodomain 2 PITX2 DNA3->PITX2 Gonadal growth DNA3->Gonadal growth Differentiation DNA3->Differentiation Placenta formation DNA3->Placenta formation node24 Left-right axis determination PITX2->node24 Mesoderm and Ectoderm PITX2->Mesoderm and Ectoderm node25 RBX1 CUL1 SKP1 node25->node18 node25->Ubiquitin mediated proteolysis +u node32 3 Transcription factors->node32 node26->node32 node27->node32 DNA4 node28->DNA4 node30 c-MYC DNA4->node30 node29 5 node30->node29 c-MYC p15 node30->p15 G1 Arrest p15->G1 Arrest DNA5 DNA5->p15 node31->DNA5 Apoptosis ECM matric neogenesis node32->Apoptosis node32->ECM matric neogenesis Immunosupression node32->Immunosupression Neurogenesis node32->Neurogenesis node20->node18 +p node3->node4 +p node21->node18 +p node16->MAPK Signaling Pathway node16->node18 +p node16->Ubiquitin mediated proteolysis +u print "