| URN | urn:agi-ProtModification:inout-urn:agi-llid:7046:out-urn:agi-llid:4087::positive:phosphorylation |
|---|---|
| References | 132 |
| Connectivity | 2 |
| Effect | positive |
| Mechanism | phosphorylation |
| Original # of References | 132 |
| TextRef | info:pmid/9346908#abs:4 |
|---|---|
| PubYear | 1997 |
| MedlineTA | J Biol Chem |
| MedLine Reference | 9346908:3 |
| Sentence | In this report, we show that TbetaRI specifically phosphorylates Smad2 on serines 465 and 467. |
| TextRef | info:pmid/9651680#abs:4 |
|---|---|
| PubYear | 1998 |
| MedlineTA | Curr Biol |
| MedLine Reference | 9651680:3 |
| Sentence | TGF-Beta RI phosphorylates the downstream effectors Smad2 and Smad3, leading to their translocation into the nucleus. |
| TextRef | info:pmid/9662508#abs:3 |
|---|---|
| PubYear | 1998 |
| MedlineTA | Chem Biol |
| MedLine Reference | 9662508:2 |
| Sentence | Activated TGF-betaRI phosphorylates two downstream effectors, Smad2 and Smad3, leading to their translocation into the nucleus. |
| TextRef | info:pmid/12206672#abs:5 |
|---|---|
| PubYear | 2002 |
| MedlineTA | Biochemistry |
| MedLine Reference | 12206672:4 |
| Sentence | A representative compound, SB203580, inhibited in vivo Smad2 phosphorylation by TbetaR-I and affected TGFbeta-dependent transcriptional activation. |
| TextRef | info:pmid/12732634#abs:3 |
|---|---|
| PubYear | 2003 |
| MedlineTA | J Biol Chem |
| MedLine Reference | 12732634:2 |
| Sentence | Here we show that Ski can block TGF-beta signaling by interfering with the phosphorylation of Smad2 and Smad3 by the activated TGF-beta type I receptor. |
| TextRef | info:pmid/10498890#abs:3 |
|---|---|
| PubYear | 1999 |
| MedlineTA | Oncogene |
| MedLine Reference | 10498890:2 |
| Sentence | Phosphorylation of Smad2/Smad3 by activated TbetaRI is inhibited by two newly discovered members of the Smad family, Smad6 and Smad7. |
| TextRef | info:pmid/10505717#abs:3 |
|---|---|
| PubYear | 1999 |
| MedlineTA | Dig Dis Sci |
| MedLine Reference | 10505717:2 |
| Sentence | Activated TbetaRI phosphorylates Smad2, which then heterodimerizes with Smad4, translocates into the nucleus, and subsequently effects gene transcription. |
| TextRef | info:pmid/14512875#abs:10 |
|---|---|
| PubYear | 2003 |
| MedlineTA | Hepatology |
| MedLine Reference | 14512875:9 |
| Sentence | Once combined with TbetaRI-phosphorylated Smad2, the Smad3 and Smad4 complex bound to plasminogen activator inhibitor-type I promoter could enhance the transcription. |
| CellType | myofibroblasts |
| TextRef | info:pmid/17545585#abs:2 |
|---|---|
| PubYear | 2007 |
| MedlineTA | Cancer Res |
| MedLine Reference | 17545585:1 |
| Sentence | TGF-beta activates both its type I receptor (TbetaRI) and c-Jun NH2-terminal kinase (JNK), which phosphorylate Smad2 and Smad3 at the COOH-terminal (pSmad2/3C) and linker regions (pSmad2/3L). |
| TextRef | info:pmid/9335505#abs:3 |
|---|---|
| PubYear | 1997 |
| MedlineTA | Nature |
| MedLine Reference | 9335505:2 |
| Sentence | For example, Smad2 is phosphorylated by the TGF-beta type I receptor upon ligand binding, forms a heteromer with Smad4, and then translocates into the nucleus where it activates transcription. |
| Organ | Bone and Bones |
| TextRef | info:pmid/18511908#abs:2 |
|---|---|
| PubYear | 2008 |
| MedlineTA | EMBO J |
| MedLine Reference | 18511908:1 |
| Sentence | The inhibitory function of TGIF is executed in part through its ability to sequester the tumour suppressor cytoplasmic promyelocytic leukaemia in the nucleus, thereby preventing the phosphorylation of Smad2 by the activated TGF-beta type I receptor. |
| TextMods | 143: '(cPML) ' -> '' |
| CellType | Granulocyte Precursor Cells |
| TextRef | info:pmid/10438456#abs:7 |
|---|---|
| PubYear | 1999 |
| MedlineTA | J Biol Chem |
| MedLine Reference | 10438456:6 |
| Sentence | These findings indicate that genetic defects in Smad2 are sufficient to confer the invasion-promoting effect of TGF-beta and reveal that TGF-beta acts through Smad2 to induce cellular invasion by a novel mechanism that is independent of Smad2 phosphorylation by the activated TGF-beta type I receptor. |
| Organ | Colorectal Region |
| TextRef | info:pmid/11451911#abs:3 |
|---|---|
| PubYear | 2001 |
| MedlineTA | Chest |
| MedLine Reference | 11451911:2 |
| Sentence | Two receptor-activated Smad proteins, Smad2 and Smad3, are phosphorylated by the activated TGF-beta type I receptor kinase, after which they partner with the common mediator, Smad4, and are translocated to the nucleus to where they participate in transcriptional complexes to control expression of target genes. |
| Tissue | Extracellular Matrix |
| CellType | Fibroblasts |
| TextRef | info:pmid/12957874#abs:7 |
|---|---|
| PubYear | 2003 |
| MedlineTA | Front Biosci |
| MedLine Reference | 12957874:6 |
| Sentence | Upon activation, the TGF-beta type I receptor phosphorylates Smad2 and Smad3, which then form complexes with Smad4 and accumulate in the nucleus to regulate transcription of a variety of genes that encode crucial determinants of cell fate, such as cell cycle components, differentiation factors and cell adhesion molecules. |
| Organ | Bone and Bones |
| TextRef | info:pmid/15056732#body:212 |
|---|---|
| PubYear | 2004 |
| MedlineTA | Mol Endocrinol |
| MedLine Reference | 15056732:1211 |
| Sentence | Smad2 is directly phosphorylated by activated TβRI. |
| TextRef | info:pmid/17579091#body:472 |
|---|---|
| PubYear | 2007 |
| MedlineTA | J Immunol |
| MedLine Reference | 17579091:1471 |
| Sentence | TGF-βRI phosphorylates Smad2. |
| CellType | Fibroblasts |
| Organ | Lung |
| TextRef | info:pmid/15312649#body:130 |
|---|---|
| PubYear | 2004 |
| MedlineTA | Neuron |
| MedLine Reference | 15312649:1129 |
| Sentence | TβR-I phosphorylates Smad2 and Smad3. |
| Organ | Nerve |
| TextRef | info:pmid/17400764#body:68 |
|---|---|
| PubYear | 2007 |
| MedlineTA | Mol Pharmacol |
| MedLine Reference | 17400764:1067 |
| Sentence | Activated TGFβRI then phosphorylates regulatory Smads, Smad2 and Smad3. |
| TextRef | info:pmid/15798217#body:64 |
|---|---|
| PubYear | 2005 |
| MedlineTA | Mol Cell Biol |
| MedLine Reference | 15798217:1063 |
| Sentence | TβRI phosphorylates receptor Smad proteins, such as Smad2 and Smad3. |
| TextMods | 35: '(R-Smad) ' -> '' |
| TextRef | info:pmid/16778189#body:76 |
|---|---|
| PubYear | 2006 |
| MedlineTA | Cancer Res |
| MedLine Reference | 16778189:1075 |
| Sentence | Receptor-regulated Smads, Smad2 and Smad3, are phosphorylated and activated by TβRI. |
| TextRef | info:pmid/15153536#body:63 |
|---|---|
| PubYear | 2004 |
| MedlineTA | J Immunol |
| MedLine Reference | 15153536:1062 |
| Sentence | The activated TβRI directly phosphorylates Smad2 and Smad3. |
| CellType | Fibroblasts |
| TextRef | info:pmid/14722617#body:63 |
|---|---|
| PubYear | 2004 |
| MedlineTA | J Clin Invest |
| MedLine Reference | 14722617:1062 |
| Sentence | The activated TβRI directly phosphorylates Smad2 and Smad3. |
| CellType | Fibroblasts |
| TextRef | info:pmid/14600158#body:66 |
|---|---|
| PubYear | 2004 |
| MedlineTA | J Biol Chem |
| MedLine Reference | 14600158:1065 |
| Sentence | Activated TGF-βRI then directly phosphorylates Smad2 and Smad3. |
| Organ | Intestines |
| Organism | Homo sapiens |
| TextRef | info:pmid/15150118#body:51 |
|---|---|
| PubYear | 2004 |
| MedlineTA | Cancer Res |
| MedLine Reference | 15150118:1050 |
| Sentence | TβRI then phosphorylates the receptor-regulated Smads Smad2 and Smad3. |
| TextMods | 55: '(R-Smads) ' -> '' |
| CellType | Epithelial Cells |
| TextRef | info:pmid/15221015#body:151 |
|---|---|
| PubYear | 2004 |
| MedlineTA | Oncogene |
| MedLine Reference | 15221015:1150 |
| Sentence | Phosphorylation of Smad2 by TβR-I is inhibited in the presence of WWP1. |
| CellLineName | 293T |
| TextRef | info:pmid/15240694#body:218 |
|---|---|
| PubYear | 2004 |
| MedlineTA | J Immunol |
| MedLine Reference | 15240694:1217 |
| Sentence | This activated receptor complex then recruits Smad2 and Smad3, which are phosphorylated by TGF-βRI. |
| TextRef | info:pmid/15546867#body:107 |
|---|---|
| PubYear | 2005 |
| MedlineTA | J Biol Chem |
| MedLine Reference | 15546867:1106 |
| Sentence | A, the ability of ALK5 to phosphorylate Smad2 and p38 depends on its Smad-activating function. |
| TextRef | info:pmid/12191474#body:103 |
|---|---|
| PubYear | 2002 |
| MedlineTA | Mol Cell |
| MedLine Reference | 12191474:1102 |
| Sentence | Receptor-regulated Smads , Smad2 and Smad3, are directly phosphorylated and thereby activated by ALK5. |
| TextMods | 25: '(R-Smads)' -> '' |
| TextRef | info:pmid/16698802#body:94 |
|---|---|
| PubYear | 2006 |
| MedlineTA | Carcinogenesis |
| MedLine Reference | 16698802:1093 |
| Sentence | Smad2 and 3 are phosphorylated by TβRI and are commonly referred to as receptor phosphorylated Smads . |
| TextMods | 102: '(RSmads)' -> '' |
| TextRef | info:pmid/11406536#body:43 |
|---|---|
| PubYear | 2001 |
| MedlineTA | Cancer Res |
| MedLine Reference | 11406536:1042 |
| Sentence | Activated TβR-I then phosphorylates Smad2 and Smad3, which in turn heterotrimerize with Smad4. |
| TextRef | info:pmid/17158884#body:71 |
|---|---|
| PubYear | 2007 |
| MedlineTA | J Biol Chem |
| MedLine Reference | 17158884:1070 |
| Sentence | The activated TβRI in turn phosphorylates the receptor-regulated Smads , Smad2 and Smad3. |
| TextMods | 72: '(R-Smads)' -> '' |
| Organ | Bone and Bones |
| TextRef | info:pmid/17160136#body:63 |
|---|---|
| PubYear | 2007 |
| MedlineTA | J Clin Invest |
| MedLine Reference | 17160136:1062 |
| Sentence | The activated TβRI phosphorylates transcription factors Smad2 or Smad3, which then binds to Smad4. |
| TextRef | info:pmid/15623506#body:325 |
|---|---|
| PubYear | 2005 |
| MedlineTA | J Biol Chem |
| MedLine Reference | 15623506:1324 |
| Sentence | Smad2/3 are phosphorylated by the activated TβR-I, and then transported into the nucleus. |
| TextRef | info:pmid/11583628#body:93 |
|---|---|
| PubYear | 2001 |
| MedlineTA | Mol Cell |
| MedLine Reference | 11583628:1092 |
| Sentence | TβR-I phosphorylates Smad2 and Smad3 at two conserved serines at the very C terminus of each protein (Massagué, 1998). |
| TextRef | info:pmid/18566209#body:146 |
|---|---|
| PubYear | 2008 |
| MedlineTA | Mol Cancer Ther |
| MedLine Reference | 18566209:1145 |
| Sentence | Activated TβRI would then phosphorylate and activate the transcription factor/transcription coregulators, Smad2 and Smad3. |
| TextRef | info:pmid/18387885#body:184 |
|---|---|
| PubYear | 2008 |
| MedlineTA | J Lipid Res |
| MedLine Reference | 18387885:1183 |
| Sentence | In the case of TGFβ, an ALK5 TβRI phosphorylates one of the two receptor-activated Smads, Smad2 or Smad3. |
| TextRef | info:pmid/12065756#body:142 |
|---|---|
| PubYear | 2002 |
| MedlineTA | Mol Pharmacol |
| MedLine Reference | 12065756:1141 |
| Sentence | We have shown that SB-431542 efficiently inhibits the ability of activated ALK4, ALK5, and ALK7 to phosphorylate Smad2. |
| TextRef | info:pmid/18974388#body:70 |
|---|---|
| PubYear | 2008 |
| MedlineTA | Circ Res |
| MedLine Reference | 18974388:1069 |
| Sentence | Thus, ALK5 phosphorylates Smad2/Smad3, whereas ALK1 activates Smad1/Smad5.8 . |
| Tissue | Endothelium |
| CellType | Endothelial Cells |
| TextRef | info:pmid/17673906#body:64 |
|---|---|
| PubYear | 2007 |
| MedlineTA | EMBO J |
| MedLine Reference | 17673906:1063 |
| Sentence | Engagement of the receptor complex activates TβRI, which phosphorylates and activates Smad2 and Smad3 (Derynck and Zhang, 2003). |
| TextRef | info:pmid/12538652#body:221 |
|---|---|
| MedLine Reference | 12538652:1220 |
| Sentence | Upon TGF-beta binding TGF-eta receptor I/ALK5 is activated and subsequently phosphorylates Smad2/3. |
| TextRef | info:pmid/12417722#body:46 |
|---|---|
| PubYear | 2002 |
| MedlineTA | Mol Cell Biol |
| MedLine Reference | 12417722:1045 |
| Sentence | Phosphorylation of Smad2 and -3 by TβRI triggers their oligomerization with Smad4 as well as their nuclear accumulation. |
| TextRef | info:pmid/15937546#body:58 |
|---|---|
| PubYear | 2005 |
| MedlineTA | J Clin Invest |
| MedLine Reference | 15937546:1057 |
| Sentence | When TGF-β binds to a TGF-βRI/TGF-βRII complex, TGF-βRI phosphorylates Smad2 and Smad3. |
| CellType | Epithelial Cells |
| TextRef | info:pmid/11139470#body:124 |
|---|---|
| PubYear | 2001 |
| MedlineTA | Circ Res |
| MedLine Reference | 11139470:1123 |
| Sentence | Activated TβR-I propagates the TGF-β signal by phosphorylating the pathway-restricted signal transducers Smad2 and Smad3. |
| TextRef | info:pmid/15781474#body:226 |
|---|---|
| PubYear | 2005 |
| MedlineTA | J Cell Biol |
| MedLine Reference | 15781474:1225 |
| Sentence | ALK1 and ALK5 phosphorylate their downstream targets Smad1/5 or Smad2/3, respectively. |
| CellType | Neurons |
| Organ | Hippocampus |
| TextRef | info:pmid/16123808#body:278 |
|---|---|
| PubYear | 2005 |
| MedlineTA | Oncogene |
| MedLine Reference | 16123808:1277 |
| Sentence | Surprising, ERK inhibitors induced Smad2/3 phosphorylation, which was dependent on TGF-βRI signaling. |
| CellType | Megakaryocytes |
| TextRef | info:pmid/12493741#body:134 |
|---|---|
| PubYear | 2003 |
| MedlineTA | J Biol Chem |
| MedLine Reference | 12493741:1133 |
| Sentence | Overinduction of the Smad signaling pathway should be reflected by an increase in phosphorylation of Smad2 by TβRI. |
| CellLineName | 293T |
| TextRef | info:pmid/16246848#body:316 |
|---|---|
| PubYear | 2005 |
| MedlineTA | J Biol Chem |
| MedLine Reference | 16246848:1315 |
| Sentence | The receptor-regulated Smad2 and Smad3 proteins are phosphorylated by TβR-I at a C-terminal SSXS motif (57). |
| Tissue | Endothelium |
| CellType | hematopoietic cells |
| TextRef | info:pmid/10728705#body:198 |
|---|---|
| PubYear | 2000 |
| MedlineTA | Cancer Res |
| MedLine Reference | 10728705:1197 |
| Sentence | Together, these data suggest that Smad 2 is constitutively phosphorylated by TβRI upon endogenous ligand binding and constantly stimulates the 3TP promoter. |
| TextRef | info:pmid/17768179#body:156 |
|---|---|
| PubYear | 2007 |
| MedlineTA | Carcinogenesis |
| MedLine Reference | 17768179:1155 |
| Sentence | Activated TβRI then phosphorylates Smad2 and Smad3, which accumulate in the nucleus with Smad4 to activate gene expression. |
| TextRef | info:pmid/16258068#body:199 |
|---|---|
| PubYear | 2005 |
| MedlineTA | Proc Natl Acad Sci U S A |
| MedLine Reference | 16258068:1198 |
| Sentence | EN specifically interacts with TβRII and blocks its ability to activate downstream signaling, including phosphorylation of Smad2 and Smad3 by TβRI. |
| TextRef | info:pmid/14684852#body:40 |
|---|---|
| MedLine Reference | 14684852:1039 |
| Sentence | In contrast, the TGF-?/activin-responsive ALK5 and ALK4 phosphorylate the other R-Smads, Smad2 and Smad3 ( 22 ). |
| TextRef | info:pmid/18511845#body:75 |
|---|---|
| PubYear | 2008 |
| MedlineTA | J Lipid Res |
| MedLine Reference | 18511845:1074 |
| Sentence | TGFβ1-activated TβRI then recruits and phosphorylates Smad2 and Smad3 at a conserved C-terminal SSXS motif. |
| Tissue | Extracellular Matrix |
| CellType | Hepatic Stellate Cells |
| TextRef | info:pmid/12842082#body:92 |
|---|---|
| PubYear | 2003 |
| MedlineTA | Cancer Cell |
| MedLine Reference | 12842082:1091 |
| Sentence | This allows for the constitutively active TβRII kinase to transphosphorylate and activate the TβRI kinase which, in turn, phosphorylates Smad2 and Smad3. |
| TextRef | info:pmid/14762439#body:32 |
|---|---|
| PubYear | 2004 |
| MedlineTA | Oncogene |
| MedLine Reference | 14762439:1031 |
| Sentence | The cytoplasmic Smad2 and Smad3 proteins are then phosphorylated by the activated TβRI kinase, which allows them to form a heteromeric complex with Smad4. |
| TextRef | info:pmid/15467747#body:55 |
|---|---|
| PubYear | 2004 |
| MedlineTA | Oncogene |
| MedLine Reference | 15467747:1054 |
| Sentence | Smad2 and Smad3 are phosphorylated by TβRI, and then form a heterodimeric complex with Smad4 (Massague, 1998). |
| CellType | Epithelial Cells |
| TextRef | info:pmid/16123807#body:76 |
|---|---|
| PubYear | 2005 |
| MedlineTA | Oncogene |
| MedLine Reference | 16123807:1075 |
| Sentence | Upon TGF-β ligation toTβRII, the latter phosphorylates and activates TβRI, which in turn phosphorylates the receptor-activated Smads, Smad2/3. |
| TextMods | 111: 'R-Smads' -> 'receptor-activated Smads' |
| Organ | Ground substance |
| TextRef | info:pmid/14595120#body:45 |
|---|---|
| PubYear | 2004 |
| MedlineTA | Mol Biol Cell |
| MedLine Reference | 14595120:1044 |
| Sentence | On ligand binding, TβRII transphosphorylates and thereby activates TβRI, which subsequently phosphorylates receptor-regulated Smad , Smad2, and Smad3. |
| TextMods | 133: '(R-Smad)' -> '' |
| TextRef | info:pmid/16888081#body:66 |
|---|---|
| PubYear | 2006 |
| MedlineTA | J Pharmacol Exp Ther |
| MedLine Reference | 16888081:1065 |
| Sentence | ALK5 is specific for active Transforming growth factor-β and/or activin and phosphorylates Smad2 and Smad3. |
| TextMods | 28: 'TGF' -> 'Transforming growth factor' |
| CellType | Fibroblasts |
| Organ | Mesenchyme |
| TextRef | info:pmid/12456654#body:42 |
|---|---|
| PubYear | 2002 |
| MedlineTA | EMBO J |
| MedLine Reference | 12456654:1041 |
| Sentence | Upon ligand binding, TβRII phosphorylates and activates TβRI, which subsequently phosphorylates the cytoplasmic Smad2 and Smad3 proteins. |
| Tissue | Epithelium |
| Organ | Lymphatic System |
| TextRef | info:pmid/16135812#body:45 |
|---|---|
| PubYear | 2005 |
| MedlineTA | Mol Cell Biol |
| MedLine Reference | 16135812:1044 |
| Sentence | TGF-β mediates phosphorylation of TβRI by TβRII, followed by phosphorylation of the R-Smads (Smad2 and -3) by TβRI (2, 43, 65). |
| CellType | Epithelial Cells |
| TextRef | info:pmid/15900023#body:63 |
|---|---|
| PubYear | 2005 |
| MedlineTA | Am J Physiol Renal Physiol |
| MedLine Reference | 15900023:1062 |
| Sentence | For example, Smad2 and Smad3, which are directly phosphorylated and activated by ALK5, undergo homotrimerization and formation of heteromeric complexes with Smad4. |
| TextRef | info:pmid/18212064#body:54 |
|---|---|
| PubYear | 2008 |
| MedlineTA | Mol Cell Biol |
| MedLine Reference | 18212064:1053 |
| Sentence | In response to ligand binding, the TGF-β1 receptor phosphorylates Smad2 and/or Smad3, which then bind Smad4 to form active heteromeric complexes. |
| Organ | Bone and Bones |
| TextRef | info:pmid/16484320#body:173 |
|---|---|
| PubYear | 2006 |
| MedlineTA | Endocrinology |
| MedLine Reference | 16484320:1172 |
| Sentence | TGF-β type I receptor-like kinase [activin receptor-like kinase 5 (ALK5)] phosphorylated and activated TGF-β receptor-regulated Smad2/3. |
| CellType | Osteoblasts |
| TextRef | info:pmid/14580334#body:104 |
|---|---|
| PubYear | 2003 |
| MedlineTA | Mol Cell |
| MedLine Reference | 14580334:1103 |
| Sentence | The activated TβRI propagates the signal to the nucleus by phosphorylating receptor-regulated (R-) Smad2 and Smad3 at their extreme C-terminal serine residues. |
| TextRef | info:pmid/18519681#body:65 |
|---|---|
| PubYear | 2008 |
| MedlineTA | Cancer Res |
| MedLine Reference | 18519681:1064 |
| Sentence | The activated TGFβ type I receptor serine/threonine kinase phosphorylates downstream signaling molecules Smad2 and Smad3, which complex with Smad4. |
| TextRef | info:pmid/18029401#body:65 |
|---|---|
| PubYear | 2007 |
| MedlineTA | J Cell Sci |
| MedLine Reference | 18029401:1064 |
| Sentence | Activin receptor-like kinase 5 (ALK5, TGFBR1) is a widely expressed TGFβ type I receptor (Franzen et al., 1993[Go]) that phosphorylates SMAD2/SMAD3. |
| Tissue | Extracellular Matrix |
| Organ | Mesenchyme |
| TextRef | info:pmid/16533909#body:131 |
|---|---|
| PubYear | 2006 |
| MedlineTA | Mol Pharmacol |
| MedLine Reference | 16533909:1130 |
| Sentence | Receptor-regulated Smads , Smad2 or Smad3, are phosphorylated by the TGF-β type I receptor kinase, whereas Smad2 is also activated by the activin receptor. |
| TextMods | 25: '(R-Smads)' -> '' |
| Organ | Bone and Bones |
| TextRef | info:pmid/12408818#body:88 |
|---|---|
| PubYear | 2002 |
| MedlineTA | Mol Cell |
| MedLine Reference | 12408818:1087 |
| Sentence | The TGFβ type I receptor phosphorylates the receptor-regulated Smads (Smad2 and Smad3), and subsequently, a heteromeric complex with the common-mediator Smad (Smad4) is formed. |
| TextMods | 71: 'R-Smads; ' -> '' 160: 'Co-Smad; ' -> '' |
| TextRef | info:pmid/19706683#body:62 |
|---|---|
| PubYear | 2009 |
| MedlineTA | J Cell Sci |
| MedLine Reference | 19706683:1061 |
| Sentence | Activated ALK5, ALK4 and ALK7 propagate the signal into the cells by phosphorylating the downstream effector proteins Smad2 and Smad3 (ten Dijke and Arthur, 2007[Go]). |
| Organ | Blood Vessels |
| TextRef | info:pmid/15326485#body:36 |
|---|---|
| PubYear | 2004 |
| MedlineTA | Oncogene |
| MedLine Reference | 15326485:1035 |
| Sentence | Receptor-activated Smads (receptor-regulated Smads) such as Smad2 and Smad3 are phosphorylated by the activated TGF-β type I receptor (TβRI) on the C-terminal SSXS motif (Macías-Silva et al., 1996). |
| TextMods | 26: 'R-Smads' -> 'receptor-regulated Smads' |
| TextRef | info:pmid/9679059#body:200 |
|---|---|
| PubYear | 1998 |
| MedlineTA | Genes Dev |
| MedLine Reference | 9679059:1199 |
| Sentence | Under these conditions, the TβR-I and BMPR-IB kinases can phosphorylate both Smad1 and Smad2, and mutations in the L45 loop do not inhibit these reactions (Y.G. Chen and J. Massagué, unpubl.). |
| TextRef | info:pmid/17942899#body:60 |
|---|---|
| PubYear | 2007 |
| MedlineTA | Cancer Res |
| MedLine Reference | 17942899:1059 |
| Sentence | Activated TβR-I phosphorylates receptor-regulated Smads (i.e., Smad2 and Smad3), which interact with common mediator Smad (Smad4) and translocate to the nucleus. |
| TextMods | 58: 'R-Smads; ' -> '' |
| TextRef | info:pmid/12700666#body:41 |
|---|---|
| PubYear | 2003 |
| MedlineTA | Oncogene |
| MedLine Reference | 12700666:1040 |
| Sentence | The activated TβRI phosphorylates the serine residues within the conserved SSXS motif at the C-terminus of receptor-regulated Smads , such as Smad2 and Smad3 (Macías-Silva et al., 1996). |
| TextMods | 133: '(R-Smads)' -> '' |
| CellType | Hepatocytes |
| TextRef | info:pmid/12606401#body:243 |
|---|---|
| PubYear | 2003 |
| MedlineTA | Biol Reprod |
| MedLine Reference | 12606401:1242 |
| Sentence | Both ALK4 and ALK5 are known to phosphorylate Smad2 and Smad3, which in turn form complexes with Smad4 and are then translocated into the nucleus [1, 2]. |
| Organ | Brain |
| TextRef | info:pmid/15604265#body:58 |
|---|---|
| PubYear | 2004 |
| MedlineTA | Cancer Res |
| MedLine Reference | 15604265:1057 |
| Sentence | TβRI, in turn, phosphorylates Smad2 and Smad3, which then associate with Smad4 and translocate to the nucleus where they regulate gene transcription (2 , 4) . |
| Organ | Ground substance |
| TextRef | info:pmid/14517293#body:59 |
|---|---|
| PubYear | 2003 |
| MedlineTA | Mol Cell Biol |
| MedLine Reference | 14517293:1058 |
| Sentence | For instance, TβRI (ALK5), ALK4, and ALK7 phosphorylate Smad2 and Smad3 and thereby transduce TGF-β-like signals for TGF-βs, activins, and nodals. |
| Organ | Bone and Bones |
| TextRef | info:pmid/20628203#body:231 |
|---|---|
| PubYear | 2010 |
| MedlineTA | J Clin Invest |
| MedLine Reference | 20628203:1230 |
| Sentence | Almost every mammalian cell holds the capacity to secrete TGF-β as well as respond to it via its dimerizing receptors TGF-βRI/TGF-βRII, which then phosphorylate SMAD2/3 (19). |
| Organ | Immune system |
| TextRef | info:pmid/11102446#body:249 |
|---|---|
| PubYear | 2001 |
| MedlineTA | J Biol Chem |
| MedLine Reference | 11102446:1248 |
| Sentence | Peptides derived from the caveolin-1 scaffolding domain are selectively capable of inhibiting the phosphorylation of GST-SMAD2 by TβR-I (T204D) and the autophosphorylation of TβR-I (T204D)in vitro. |
| TextRef | info:pmid/12697700#body:43 |
|---|---|
| MedLine Reference | 12697700:1042 |
| Sentence | Upon activation by TbetaRII, the TbetaRI phosphorylates an R-Smad (Smad 2 or 3), allowing it to associate with a common mediator Smad (Smad 4), forming a hetero-oligomeric complex, which translocates to the nucleus. |
| TextRef | info:pmid/10393693#body:77 |
|---|---|
| PubYear | 1999 |
| MedlineTA | J Clin Invest |
| MedLine Reference | 10393693:1076 |
| Sentence | This phosphorylated peptide corresponds to the phosphorylation sites of Smad2, and the antibody specifically recognizes Smad2 phosphorylated by the TGF-β type I receptor (22). |
| Tissue | Blood |
| Organ | Lung |
| TextRef | info:pmid/12660320#body:67 |
|---|---|
| PubYear | 2003 |
| MedlineTA | J Am Soc Nephrol |
| MedLine Reference | 12660320:1066 |
| Sentence | After TGF-β binding to its receptors, the receptor-regulated Smads , Smad2 and Smad3, are phosphorylated by the TGF-β type I receptor and associate with a common partner, Smad4. |
| TextMods | 68: '(R-Smads)' -> '' |
| Organ | Kidney Glomerulus |
| TextRef | info:pmid/11927558#body:99 |
|---|---|
| MedLine Reference | 11927558:1098 |
| Sentence | These data suggest that there are two signalling pathways downstream of TGF-? in ECs, one through ALK5 phosphorylating Smad2 and the other via ALK1 leading to Smad1/5 phosphorylation. |
| TextRef | info:pmid/16818646#body:67 |
|---|---|
| PubYear | 2006 |
| MedlineTA | Cancer Res |
| MedLine Reference | 16818646:1066 |
| Sentence | Activated TβRI in turn phosphorylates Smad2 and Smad3, which interact with Smad4, translocate to the nucleus, and regulate transcription of target genes. |
| CellType | Epithelial Cells |
| Organ | Mammary Gland |
| Organism | Homo sapiens |
| TextRef | info:pmid/15178549#body:296 |
|---|---|
| PubYear | 2004 |
| MedlineTA | Am J Physiol Gastrointest Liver Physiol |
| MedLine Reference | 15178549:1295 |
| Sentence | Once activated by TGF-β1-dependent association with TGF-βRII, TGF-βRI phosphorylates its primary receptor-coupled Smad substrates, Smad2 and/or Smad3 (36). |
| TextMods | 100: 'R-Smad ' -> 'receptor-coupled Smad ' |
| CellType | Myocytes, Smooth Muscle |
| Organ | Intestines |
| Organism | Homo sapiens |
| TextRef | info:pmid/19841540#body:62 |
|---|---|
| PubYear | 2009 |
| MedlineTA | J Clin Invest |
| MedLine Reference | 19841540:1061 |
| Sentence | TGFβRI is phosphorylated within its GS region (i.e., SGSGSG sequence) by TGFβRII, allowing it to phosphorylate downstream receptor-regulated Smads — Smad2 and Smad3 — at their C-terminal SSXS motif (10, 11). |
| TextMods | 149: '(R-Smads) ' -> '' |
| Organ | Bone and Bones |
| TextRef | info:pmid/15855236#body:59 |
|---|---|
| PubYear | 2005 |
| MedlineTA | J Cell Sci |
| MedLine Reference | 15855236:1058 |
| Sentence | Binding of TGF-β to the TGF-β receptor II (TβRII) activates the signal-transducing TGF-β receptor I (TβRI) that phosphorylates latent cytoplasmic transcriptional activators, Smad2 and Smad3. |
| CellType | Fibroblasts |
| TextRef | info:pmid/12488458#body:52 |
|---|---|
| PubYear | 2003 |
| MedlineTA | J Biol Chem |
| MedLine Reference | 12488458:1051 |
| Sentence | The cytokine binds to TGFBR-2, which then phosphorylates and activates the TGFBR-1 kinase (1, 32), which, in turn, phosphorylates the receptor-associated Smad2 and Smad3 proteins. |
| CellType | Epithelial Cells |
| Organ | Prostate |
| TextRef | info:pmid/12853969#body:35 |
|---|---|
| PubYear | 2003 |
| MedlineTA | Oncogene |
| MedLine Reference | 12853969:1034 |
| Sentence | Upon ligand binding, TβR-II phosphorylates and activates TβR-I, which directly phosphorylates the receptor-regulated R-Smads (Smad2 and Smad3), which then form a hetero-oligomer with Co-Smad (Smad4). |
| TextRef | info:pmid/19325136#body:42 |
|---|---|
| PubYear | 2009 |
| MedlineTA | Carcinogenesis |
| MedLine Reference | 19325136:1041 |
| Sentence | The serine/threonine kinase TβRI then directly phosphorylates Smad2 and Smad3, which form a complex with Smad4, accumulates in the nucleus and regulates gene transcription (7). |
| TextRef | info:pmid/14755243#body:39 |
|---|---|
| PubYear | 2004 |
| MedlineTA | Oncogene |
| MedLine Reference | 14755243:1038 |
| Sentence | Mature TGFβ binds to TGFβ type II receptor (TβRII), which phosphorylates and activates a TGFβ type I receptor (TβRI), which in turn phosphorylates Smad2 and Smad3 proteins (Massague et al., 2000). |
| Organ | Mesenchyme |
| TextRef | info:pmid/10559198#body:58 |
|---|---|
| PubYear | 1999 |
| MedlineTA | J Biol Chem |
| MedLine Reference | 10559198:1057 |
| Sentence | C-terminal phosphorylation of Smad2 or Smad3 by TβRI results in a conformational change that promotes heteromerization with Smad4, and stimulates nuclear translocation of Smad complexes. |
| Tissue | Adipose tissue |
| CellType | Adipocytes |
| TextRef | info:pmid/14670985#body:63 |
|---|---|
| PubYear | 2004 |
| MedlineTA | Endocrinology |
| MedLine Reference | 14670985:1062 |
| Sentence | Consequently, TβRI phosphorylates the receptor-associated proteins, Smad 2 and/or Smad 3, which are then released from the receptor site to form a new heteromer with Smad 4. |
| CellType | Neurons |
| Organ | hypothalamus |
| TextRef | info:pmid/11779503#body:396 |
|---|---|
| PubYear | 2001 |
| MedlineTA | Mol Cell |
| MedLine Reference | 11779503:1395 |
| Sentence | In fact, as the receptor complex contains two molecules of TβRI, which likely binds and phosphorylates two Smad2 molecules simultaneously, the phosphorylated Smad2 molecules might help each other to dissociate from the receptor complex. |
| TextRef | info:pmid/9765209#body:241 |
|---|---|
| PubYear | 1998 |
| MedlineTA | Genes Dev |
| MedLine Reference | 9765209:1240 |
| Sentence | The constitutively active TβRI phosphorylates Smad2 and Smad3, which are normally phosphorylated by the wild-type I receptor only on addition of TGF-β (Macias-Silva et al. 1996; Abdollah et al. 1997; Souchenlnytskyi et al. 1997). |
| TextRef | info:pmid/18625725#body:50 |
|---|---|
| PubYear | 2008 |
| MedlineTA | Mol Cell Biol |
| MedLine Reference | 18625725:1049 |
| Sentence | Activated TβRI can phosphorylate the transcription factors Smad2 and Smad3, which then associate with Smad4 and translocate to the nucleus, where they regulate gene transcription (36). |
| CellType | Fibroblasts |
| Organism | Mus musculus |
| TextRef | info:pmid/9346966#body:247 |
|---|---|
| PubYear | 1997 |
| MedlineTA | J Biol Chem |
| MedLine Reference | 9346966:1246 |
| Sentence | Upon TGF-β stimulation, Smad2 and Smad3 are directly phosphorylated by the TβR-I kinase and form heteromeric complexes with Smad4 that are translocated from the cytoplasm to the nucleus. |
| TextRef | info:pmid/11070163#body:141 |
|---|---|
| PubYear | 2000 |
| MedlineTA | Immunity |
| MedLine Reference | 11070163:1140 |
| Sentence | Binding of TGF-β to TβRII leads to recruitment and activation of TβRI, which in turn binds and phosphorylates cytosolic signal transducers of the SMAD family, Smad2 and Smad3 (Heldin et al. 1997). |
| CellType | B-Lymphocytes |
| TextRef | info:pmid/14500687#body:50 |
|---|---|
| PubYear | 2003 |
| MedlineTA | J Immunol |
| MedLine Reference | 14500687:1049 |
| Sentence | Following the phosphorylation of Smad2 or Smad3 by the activated TbetaRI, a heteromeric complex is formed with Smad4, resulting in translocation of the complex into the nucleus (6, 7). |
| Tissue | Extracellular Matrix |
| CellType | Fibroblasts |
| Organ | Skin |
| TextRef | info:pmid/16314499#body:54 |
|---|---|
| PubYear | 2005 |
| MedlineTA | Mol Cell Biol |
| MedLine Reference | 16314499:1053 |
| Sentence | Upon binding of TGF-β1, the type I TGF-β receptor kinase (TβRI) becomes activated by the type II receptor kinase and phosphorylates two highly related cytoplasmic Smad proteins, Smad2 and Smad3. |
| CellType | Fibroblasts |
| TextRef | info:pmid/12065755#body:227 |
|---|---|
| PubYear | 2002 |
| MedlineTA | Mol Pharmacol |
| MedLine Reference | 12065755:1226 |
| Sentence | ALK5 then phosphorylates Ser465and Ser467 of the conserved C-terminal end of Smad2 (Abdollah et al., 1997; Souchelnytskyi et al., 1997), and this phosphorylation of Smad2 is required for its nuclear accumulation and signaling (Macias-Silva et al., 1996). |
| TextRef | info:pmid/12065756#body:95 |
|---|---|
| MedLine Reference | 12065756:1094 |
| Sentence | As expected, activated ALK4, ALK5, and ALK7 all efficiently phosphorylated Smad2 (Fig. 1 B, top). |
| CellLineName | NIH 3T3 |
| Journal | Mol. Pharm |
| Journal Reference | v62 i1 p65 (2002) |
| Journal Link | http://molpharm.aspetjournals.org/cgi/content/full/62/1/65 |
| Source | Ariadne Signaling Pathways |
| TextRef | info:pmid/15180923#body:225 |
|---|---|
| MedLine Reference | 15180923:1224 |
| Sentence | On activation, the TGF-beta type I receptor induces Smad-2/3 phosphorylation, which then forms complexes with Smad-4, translocates into nuclei, and controls the transcription of TGF-beta-responsive genes. |
| Organ | Kidney |
| Journal | Renal Phys |
| Journal Reference | v287 i1 pF7 (2004) |
| Journal Link | http://ajprenal.physiology.org/cgi/content/full/287/1/F7 |
| Source | Ariadne Signaling Pathways |
| TextRef | info:pmid/14978253#body:89 |
|---|---|
| MedLine Reference | 14978253:1088 |
| Sentence | In the canonical signaling pathway, Smad1 is phosphorylated by active ALK1, ALK2, ALK3, and ALK6, whereas Smad2 is activated by ALK4, ALK5, and ALK7 (Watanabe et al., 1999 ; Piek and Roberts, 2001 ). |
| CellLineName | COS I |
| Journal | Mol. Pharm |
| Journal Reference | v65 i3 p744 (2004) |
| Journal Link | http://molpharm.aspetjournals.org/cgi/content/full/65/3/744 |
| Source | Ariadne Signaling Pathways |
| TextRef | info:pmid/10465304#body:249 |
|---|---|
| MedLine Reference | 10465304:1248 |
| Sentence | Recently, Shimizu et al. ( 35 ) reported that TGF-beta1 signaling through TbetaR-I activated Smad2 and Smad3, but activin signaling through ActR-IB activated predominantly Smad3 in human keratinocytes. |
| CellType | keratinocyte |
| Journal | Endocrinology |
| Journal Reference | v140 i9 p4300 (1999) |
| Journal Link | http://endo.endojournals.org/cgi/content/full/140/9/4300 |
| Source | Ariadne Signaling Pathways |
| TextRef | info:pmid/11019486#abs:4 |
|---|---|
| MedLine Reference | 11019486:3 |
| Tissue | endothelial |
| Source | Ariadne Signaling Pathways |
| TextRef | info:pmid/14580334#abs:2 |
|---|---|
| MedLine Reference | 14580334:1 |
| Tissue | endothelial |
| Source | Ariadne Signaling Pathways |
| TextRef | info:pmid/11058129#abs:2 |
|---|---|
| MedLine Reference | 11058129:1 |
| Source | Ariadne Signaling Pathways |
| MedLine Reference | 0:62183001 |
|---|---|
| Source | Ariadne Signaling Pathways |
| TextRef | info:pmid/12732634#body:189 |
|---|---|
| MedLine Reference | 12732634:1188 |
| Journal | J. Biol. Chem |
| Journal Reference | v278 i28 p26249 (2003) |
| Journal Link | http://www.jbc.org/cgi/content/full/278/28/26249 |
| Source | Ariadne Signaling Pathways |
| TextRef | info:pmid/10716993#body:170 |
|---|---|
| MedLine Reference | 10716993:1169 |
| CellLineName | COS |
| Journal | PNAS |
| Journal Reference | v97 i6 p2626 (2000) |
| Journal Link | http://www.pnas.org/cgi/content/full/97/6/2626 |
| Source | Ariadne Signaling Pathways |
| TextRef | info:pmid/9261125#abs:8 |
|---|---|
| MedLine Reference | 9261125:7 |
| Tissue | epithelia |
| Organ | Lung |
| Source | Ariadne Signaling Pathways |
| TextRef | info:pmid/9215638#abs:5 |
|---|---|
| MedLine Reference | 9215638:4 |
| Source | Ariadne Signaling Pathways |
| TextRef | info:pmid/9311995#abs:4 |
|---|---|
| MedLine Reference | 9311995:3 |
| Source | Ariadne Signaling Pathways |
| TextRef | info:pmid/15867212#abs:2 |
|---|---|
| MedLine Reference | 15867212:1 |
| Source | Ariadne Signaling Pathways |
| TextRef | info:pmid/12221115#body:161 |
|---|---|
| MedLine Reference | 12221115:1160 |
| Tissue | endothelial |
| Journal | Mol. Biol. Cell |
| Journal Reference | v13 i9 p3055 (2002) |
| Journal Link | http://www.molbiolcell.org/cgi/content/full/13/9/3055 |
| Source | Ariadne Signaling Pathways |
| TextRef | info:pmid/15210694#body:90 |
|---|---|
| MedLine Reference | 15210694:1089 |
| Journal | J. Biol. Chem |
| Journal Reference | v279 i34 p35781 (2004) |
| Journal Link | http://www.jbc.org/cgi/content/full/279/34/35781 |
| Source | Ariadne Signaling Pathways |
| TextRef | info:pmid/12547835#body:36 |
|---|---|
| MedLine Reference | 12547835:1035 |
| Journal | J. Biol. Chem |
| Journal Reference | v278 i13 p11721 (2003) |
| Journal Link | http://www.jbc.org/cgi/content/full/278/13/11721 |
| Source | Ariadne Signaling Pathways |
| TextRef | info:pmid/14517293#body:42 |
|---|---|
| MedLine Reference | 14517293:1041 |
| Journal | Mol. Cell. Biol |
| Journal Reference | v23 i20 p7230 (2003) |
| Journal Link | http://mcb.asm.org/cgi/content/full/23/20/7230 |
| Source | Ariadne Signaling Pathways |
| TextRef | info:pmid/12637528#body:26 |
|---|---|
| MedLine Reference | 12637528:1025 |
| Journal | J. Biol. Chem |
| Journal Reference | v278 i20 p18069 (2003) |
| Journal Link | http://www.jbc.org/cgi/content/full/278/20/18069 |
| Source | Ariadne Signaling Pathways |
| TextRef | info:pmid/15689496#body:170 |
|---|---|
| MedLine Reference | 15689496:1169 |
| CellLineName | nmumg |
| Journal | Mol. Biol. Cell |
| Journal Reference | v16 i4 p1987 (2005) |
| Journal Link | http://www.molbiolcell.org/cgi/content/full/16/4/1987 |
| Source | Ariadne Signaling Pathways |
| TextRef | info:pmid/15034041#body:218 |
|---|---|
| MedLine Reference | 15034041:1217 |
| CellLineName | MODE |
| CellType | T-cell |
| Journal | J. Immunol |
| Journal Reference | v172 i7 p4275 (2004) |
| Journal Link | http://www.jimmunol.org/cgi/content/full/172/7/4275 |
| Source | Ariadne Signaling Pathways |
| TextRef | info:pmid/10667205#abs:3 |
|---|---|
| MedLine Reference | 10667205:2 |
| Source | Ariadne Signaling Pathways |
| TextRef | info:pmid/15923183#cont:37 |
|---|---|
| MedLine Reference | 15923183:10036 |
| Journal | J. Biol. Chem |
| Journal Reference | v280 i30 p27800 |
| Journal Link | http://www.jbc.org/cgi/content/full/280/30/27800 |
| Source | Ariadne Signaling Pathways |
| TextRef | info:pmid/15148321#cont:25 |
|---|---|
| MedLine Reference | 15148321:10024 |
| Journal | J. Biol. Chem |
| Journal Reference | v279 i30 p31568 |
| Journal Link | http://www.jbc.org/cgi/content/full/279/30/31568 |
| Source | Ariadne Signaling Pathways |
| TextRef | info:pmid/15769863#cont:245 |
|---|---|
| MedLine Reference | 15769863:10244 |
| Journal | JPET |
| Journal Reference | v313 i3 p943 |
| Journal Link | http://jpet.aspetjournals.org/cgi/content/full/313/3/943 |
| Source | Ariadne Signaling Pathways |
| TextRef | info:pmid/14688282#cont:123 |
|---|---|
| MedLine Reference | 14688282:10122 |
| Journal | J. Biol. Chem |
| Journal Reference | v279 i10 p8873 |
| Journal Link | http://www.jbc.org/cgi/content/full/279/10/8873 |
| Source | Ariadne Signaling Pathways |
| TextRef | info:pmid/12193547#cont:254 |
|---|---|
| MedLine Reference | 12193547:10253 |
| Journal | Endocrinology |
| Journal Reference | v143 i9 p3351 |
| Journal Link | http://endo.endojournals.org/cgi/content/full/143/9/3351 |
| Source | Ariadne Signaling Pathways |
| TextRef | info:pmid/12606401#cont:182 |
|---|---|
| MedLine Reference | 12606401:10181 |
| Journal | Biology of reproduction |
| Journal Reference | v68 i5 p1719 |
| Journal Link | http://www.biolreprod.org/cgi/content/full/68/5/1719 |
| Source | Ariadne Signaling Pathways |
| TextRef | info:pmid/15817471#cont:35 |
|---|---|
| MedLine Reference | 15817471:10034 |
| Journal | J. Biol. Chem |
| Journal Reference | v280 i23 p22115 |
| Journal Link | http://www.jbc.org/cgi/content/full/280/23/22115 |
| Source | Ariadne Signaling Pathways |
| TextRef | info:pmid/15781474#cont:204 |
|---|---|
| MedLine Reference | 15781474:10203 |
| Journal | J. Cell Biol |
| Journal Reference | v168 i7 p1077 |
| Journal Link | http://www.jcb.org/cgi/content/full/168/7/1077 |
| Source | Ariadne Signaling Pathways |
| TextRef | info:pmid/15546867#cont:71 |
|---|---|
| MedLine Reference | 15546867:10070 |
| Journal | J. Biol. Chem |
| Journal Reference | v280 i4 p2644 |
| Journal Link | http://www.jbc.org/cgi/content/full/280/4/2644 |
| Source | Ariadne Signaling Pathways |
| TextRef | info:pmid/15843168#abs:8 |
|---|---|
| MedLine Reference | 15843168:7 |
| CellLineName | MCF7 |
| Source | Ariadne Signaling Pathways |