| URN | urn:agi-ProtModification:inout-urn:agi-llid:7046:out-urn:agi-llid:4088::positive:phosphorylation |
|---|---|
| References | 127 |
| Connectivity | 2 |
| Effect | positive |
| Mechanism | phosphorylation |
| Original # of References | 127 |
| TextRef | info:pmid/10667205#abs:3 |
|---|---|
| MedLine Reference | 10667205:2 |
| Sentence | Smads 2 and 3 are phosphorylated by the TGF-beta type I receptor. |
| 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/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/20060813#abs:2 |
|---|---|
| PubYear | 2010 |
| MedlineTA | Biochem Biophys Res Commun |
| MedLine Reference | 20060813:1 |
| Sentence | ALK-1 phosphorylates transcription factors SMAD1/5, which bind to BMP-responsive elements , whereas ALK-5 phosphorylates SMAD3, which binds to CAGA elements. |
| TextMods | 90: '(BRE)' -> '' |
| TextRef | info:pmid/11438668#abs:7 |
|---|---|
| PubYear | 2001 |
| MedlineTA | Mol Cell Biol |
| MedLine Reference | 11438668:6 |
| Sentence | Upon receptor activation, Smad3 was strongly phosphorylated by TGF-beta type I receptor (TbetaR-I) in the presence of Axin, and dissociated from TbetaR-I and Axin. |
| TextRef | info:pmid/12065755#abs:5 |
|---|---|
| PubYear | 2002 |
| MedlineTA | Mol Pharmacol |
| MedLine Reference | 12065755:4 |
| Sentence | The p38 mitogen-activated protein kinase inhibitors SB-203580 and SB-202190 also inhibit phosphorylation of Smad3 by ALK5 with IC50 values of 6 and 3 microM, respectively. |
| Tissue | Extracellular Matrix |
| 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/19263472#abs:3 |
|---|---|
| PubYear | 2009 |
| MedlineTA | Hepatology |
| MedLine Reference | 19263472:2 |
| Sentence | TGF-beta activates TGF-beta type I receptor (TbetaRI) and c-Jun N-terminal kinase (JNK), which differentially phosphorylate the mediator Smad3 to become C-terminally phosphorylated Smad3 (pSmad3C) and linker-phosphorylated Smad3 (pSmad3L). |
| TextRef | info:pmid/19418558#abs:2 |
|---|---|
| PubYear | 2009 |
| MedlineTA | Hepatology |
| MedLine Reference | 19418558:1 |
| Sentence | TGF-beta activates the TGF-beta type I receptor (TbetaRI) and c-Jun N-terminal kinase (JNK), which differentially phosphorylate the mediator Smad3 to become COOH-terminally phosphorylated Smad3 (pSmad3C) and linker-phosphorylated Smad3 (pSmad3L). |
| TextRef | info:pmid/10559222#abs:8 |
|---|---|
| MedLine Reference | 10559222:7 |
| Sentence | In human embryonic kidney 293 cells, the expression of constitutively active TGF-beta type I receptor was able to induce the formation of a Smad3- and Smad4-containing nuclear protein complex that bound the SBE. |
| 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/15312649#body:130 |
|---|---|
| PubYear | 2004 |
| MedlineTA | Neuron |
| MedLine Reference | 15312649:1129 |
| Sentence | TβR-I phosphorylates Smad2 and Smad3. |
| Organ | Nerve |
| TextRef | info:pmid/18239144#body:63 |
|---|---|
| PubYear | 2008 |
| MedlineTA | Circ Res |
| MedLine Reference | 18239144:1062 |
| Sentence | TβRI phosphorylates Smad3 at the S423/S425 within the C-terminal MH2. |
| 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/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/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/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/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/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/15009204#body:288 |
|---|---|
| PubYear | 2004 |
| MedlineTA | Eur J Biochem |
| MedLine Reference | 15009204:1287 |
| Sentence | This modification in turn promotes TβRI-dependent C-terminal phosphorylation of Smad3 [29]. |
| CellLineName | PC 12 |
| 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/11118211#body:159 |
|---|---|
| PubYear | 2000 |
| MedlineTA | EMBO J |
| MedLine Reference | 11118211:1158 |
| Sentence | It is known that the TGF-β type I receptor kinase directly phosphorylates Smad3 at the C-terminal SSVS motif. |
| 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/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/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/10601313#body:228 |
|---|---|
| PubYear | 1999 |
| MedlineTA | J Biol Chem |
| MedLine Reference | 10601313:1227 |
| Sentence | Phosphorylation of Smad3 by TβRI occurs on the C-terminal -SSXS motif and is necessary for its efficient nuclear translocation (34, 35). |
| 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/15034041#body:30 |
|---|---|
| MedLine Reference | 15034041:1029 |
| Sentence | Smad2 and Smad3 are directly phosphorylated and activated by TbetaRI and heterodimerize with Smad4. |
| 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/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/18757436#body:254 |
|---|---|
| PubYear | 2008 |
| MedlineTA | Cancer Res |
| MedLine Reference | 18757436:1253 |
| Sentence | The activated TβRI phosphorylates Smad3, which then enters into the nucleus and directly inhibits c-Myc and telomerase activity (22). |
| 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/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/18321991#body:179 |
|---|---|
| PubYear | 2008 |
| MedlineTA | Mol Biol Cell |
| MedLine Reference | 18321991:1178 |
| Sentence | Because activated TβRI directly phosphorylates Smad3 on its C-terminal serine residues, we tested whether p130Cas interferes with the phosphorylation of Smad3 by TβRI. |
| CellLineName | HaCat |
| 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/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/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/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/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/11102446#body:211 |
|---|---|
| PubYear | 2001 |
| MedlineTA | J Biol Chem |
| MedLine Reference | 11102446:1210 |
| Sentence | The ligand-activated TβR-I directly phosphorylates Smad-2 and -3 at a C-terminal SSXS motif (7, 68), a modification that facilitates Smad-2/-3 release and subsequent heteromerization with Smad-4 (9, 69). |
| 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/11571638#body:183 |
|---|---|
| PubYear | 2001 |
| MedlineTA | Oncogene |
| MedLine Reference | 11571638:1182 |
| Sentence | This occurs naturally by the phosphorylation of Smad3 by TGFβ-type I receptor or can be achieved artificially when the C-terminus, the MH2 domain, is removed (Kawabata et al., 1998; Song et al., 1998, Zawel et al., 1998). |
| CellLineName | HepG 2 |
| 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/12639945#body:206 |
|---|---|
| PubYear | 2003 |
| MedlineTA | Endocrinology |
| MedLine Reference | 12639945:1205 |
| Sentence | Because the luciferase activity from AR3-Lux in these transfected cells was increased by TGF-β stimulation (data not shown), Smad3 may be phosphorylated by the TGF-β type I receptor in KGN cells. |
| CellLineName | KGN |
| 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/12773577#body:359 |
|---|---|
| PubYear | 2003 |
| MedlineTA | Mol Cell Biol |
| MedLine Reference | 12773577:1358 |
| Sentence | After TGFβ binds to its receptors, activated TβRI phosphorylates Smad2 and Smad3, which then forms a complex with Smad4 and translocates to the nucleus to propagate TGFβ signaling (35). |
| Tissue | Serum |
| Organ | Fetus |
| TextRef | info:pmid/10535941#body:86 |
|---|---|
| PubYear | 1999 |
| MedlineTA | Proc Natl Acad Sci U S A |
| MedLine Reference | 10535941:1085 |
| Sentence | As previously described, we generated a mutant version of Smad3, termed Smad3D, in which we converted the three C-terminal serines into aspartic acid residues to mimic the physiologic phosphorylation of Smad3 by the activated TGF-β type I receptor kinase (30). |
| TextRef | info:pmid/17875924#body:69 |
|---|---|
| PubYear | 2007 |
| MedlineTA | Mol Cell Biol |
| MedLine Reference | 17875924:1068 |
| Sentence | In turn, activated TGF-βRI phosphorylates the receptor-regulated proteins SMAD2 and SMAD3, which then associate with the common mediator SMAD (SMAD4), translocate to the nucleus, and induce transcriptional activation (29). |
| 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. |
| TextRef | info:pmid/19096363#body:41 |
|---|---|
| PubYear | 2009 |
| MedlineTA | EMBO J |
| MedLine Reference | 19096363:1040 |
| Sentence | The selectivity of Smad2/3 phosphorylation by ALK5 is ensured by the kinase domain-embedded L45 loop, which is thought to serve as the docking site for Smad2/3 (Feng and Derynck, 1997; Chen et al, 1998; Itoh et al, 2003). |
| CellType | Epithelial Cells |
| Organ | Mammary Gland |
| TextRef | info:pmid/11927558#body:34 |
|---|---|
| MedLine Reference | 11927558:1033 |
| Sentence | Interestingly, while activated ALK5 induces the phosphorylation of Smad2 and Smad3, activated ALK1 has been shown to induce the phosphorylation of Smad1 and Smad5 in transfected COS cells ( Chen and Massagu?, 1999 ; Oh et al ., 2000 ). |
| CellLineName | COS |
| Journal | EMBO |
| Journal Reference | v21 i7 p1743 (2002) |
| Journal Link | http://embojournal.npgjournals.com/cgi/content/full/21/7/1743 |
| Source | Ariadne Signaling Pathways |
| TextRef | info:pmid/14688282#body:124 |
|---|---|
| MedLine Reference | 14688282:1123 |
| Sentence | In COS7 cells, the expression of dominant-negative Smad2/3 has been shown to inhibit both Smad2- and Smad3-dependent TGF-beta signaling pathways by blocking Smad2 and Smad3 phosphorylation by TGF-beta type 1 receptor ( 13 ). |
| CellLineName | COS-7 |
| Journal | J. Biol. Chem |
| Journal Reference | v279 i10 p8873 (2004) |
| Journal Link | http://www.jbc.org/cgi/content/full/279/10/8873 |
| Source | Ariadne Signaling Pathways |
| TextRef | info:pmid/12876289#body:228 |
|---|---|
| MedLine Reference | 12876289:1227 |
| Sentence | Thus, the possibility that p70S6 kinase, activated by IGF-I, suppresses the activation of Smad3 by TGF-beta would suggest that the association of protein phosphatase 2A to the activated TbetaRI may function to further enhance Smad3 activation by relieving this suppression of p70S6 kinase. |
| Journal | J. Biol. Chem |
| Journal Reference | v278 i40 p38342 (2003) |
| Journal Link | http://www.jbc.org/cgi/content/full/278/40/38342 |
| Source | Ariadne Signaling Pathways |
| TextRef | info:pmid/12707256#body:43 |
|---|---|
| MedLine Reference | 12707256:1042 |
| Sentence | Much interest has focused on defining the role of the Smad family of proteins in TGFbeta signaling ( 3 ), showing that the activated kinase of TbetaRI phosphorylates Smad3, which then associates with Smad4 to form complexes that determine many of the effects of TGFbeta on transcriptional activation. |
| Tissue | endothelial |
| Journal | J. Biol. Chem |
| Journal Reference | v278 i27 p25109 (2003) |
| Journal Link | http://www.jbc.org/cgi/content/full/278/27/25109 |
| 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 | 0:07398533 |
|---|---|
| Source | Ariadne Signaling Pathways |
| TextRef | info:pmid/9311995#abs:4 |
|---|---|
| MedLine Reference | 9311995:3 |
| Source | Ariadne Signaling Pathways |
| TextRef | info:pmid/12538652#body:221 |
|---|---|
| MedLine Reference | 12538652:1220 |
| CellLineName | PANC1 |
| Journal | J. Biol. Chem |
| Journal Reference | v278 i13 p11041 (2003) |
| Journal Link | http://www.jbc.org/cgi/content/full/278/13/11041 |
| Source | Ariadne Signaling Pathways |
| TextRef | info:pmid/14512875#abs:11 |
|---|---|
| MedLine Reference | 14512875:10 |
| Organ | Liver |
| Source | Ariadne Signaling Pathways |
| TextRef | info:pmid/15867212#abs:2 |
|---|---|
| MedLine Reference | 15867212:1 |
| Source | Ariadne Signaling Pathways |
| TextRef | info:pmid/11243848#abs:5 |
|---|---|
| MedLine Reference | 11243848:4 |
| Source | Ariadne Signaling Pathways |
| TextRef | info:pmid/11019486#abs:4 |
|---|---|
| MedLine Reference | 11019486:3 |
| Tissue | endothelial |
| 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/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/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/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/10465304#body:248 |
|---|---|
| MedLine Reference | 10465304:1247 |
| 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/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 |
| MedLine Reference | 4193855726 |
|---|---|
| CellLineName | KGN |
| Journal | Endocrinology |
| Journal Reference | v144 i4 p1603 (1997) |
| Journal Link | http://endo.endojournals.org/cgi/content/full/144/4/1603 |
| Source | Ariadne Signaling Pathways |
| MedLine Reference | 2430720634 |
|---|---|
| CellLineName | KGN |
| Journal | Endocrinology |
| Journal Reference | v144 i4 p1603 (1997) |
| Journal Link | http://endo.endojournals.org/cgi/content/full/144/4/1603 |
| Source | Ariadne Signaling Pathways |
| MedLine Reference | 125004465:11182 |
|---|---|
| Journal | Endocrinology |
| Journal Reference | v144 i4 p1603 |
| Journal Link | http://endo.endojournals.org/cgi/content/full/144/4/1603 |
| 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/12547835#cont:36 |
|---|---|
| MedLine Reference | 12547835:10035 |
| Journal | J. Biol. Chem |
| Journal Reference | v278 i13 p11721 |
| Journal Link | http://www.jbc.org/cgi/content/full/278/13/11721 |
| 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 |