| RRC ID |
37766
|
| Author |
Murakami M, Kawachi H, Ogawa K, Nishino Y, Funaba M.
|
| Title |
Receptor expression modulates the specificity of transforming growth factor-beta signaling pathways.
|
| Journal |
Genes Cells
|
| Abstract |
In current models of transforming growth factor-beta (TGF-beta) family signaling, type II receptors activate specific activin receptor-like kinase (ALK) type I receptors. These serine/threonine kinases activate ligand-dependent receptor regulated (R)-Smad by phosphorylating carboxy-terminal serines. We found that the receptor expression levels affected the phosphorylation and activation of the two R-Smad subclasses, activin/TGF-beta-specific (AR-Smad) and bone morphogenetic protein (BMP)-specific (BR-Smad). Co-expressing constitutively active type I and type II receptors in COS7 cells resulted in the phosphorylation of both R-Smad subclasses in a ligand-independent manner. This was verified using in vitro kinase assays. In untransfected B16 melanoma cells, TGF-beta1 and BMP-2 induced phosphorylation of both R-Smad subclasses, and TGF-beta1 up-regulated the inhibitor of differentiation (Id) gene, which is usually regulated by BMP. By contrast, BMP-2 up-regulated plasminogen activator inhibitor-1 (PAI-1), which is an AR-Smad-regulated gene. Except for ALK4 and ALK6, levels of type I and type II receptor mRNAs were higher in B16 cells than in HeLa and HepG2 cells, in which TGF-beta1 and BMP-2 induced phosphorylation of only the expected R-Smad. These results help to explain the diverse effects of this ligand family.
|
| Volume |
14(4)
|
| Pages |
469-82
|
| Published |
2009-4-1
|
| DOI |
10.1111/j.1365-2443.2009.01283.x
|
| PII |
GTC1283
|
| PMID |
19335617
|
| MeSH |
Activin Receptors, Type I / genetics
Activin Receptors, Type I / metabolism*
Animals
Blotting, Western
Bone Morphogenetic Protein 2 / pharmacology
COS Cells
Cell Line
Cell Line, Tumor
Chlorocebus aethiops
Dose-Response Relationship, Drug
Gene Expression
HeLa Cells
Humans
Imidazoles / pharmacology
Immunoprecipitation
Mice
Phosphorylation / drug effects
Protein Serine-Threonine Kinases / genetics
Protein Serine-Threonine Kinases / metabolism*
Pyridines / pharmacology
RNA Interference
Receptor, Transforming Growth Factor-beta Type II
Receptors, Transforming Growth Factor beta / genetics
Receptors, Transforming Growth Factor beta / metabolism*
Reverse Transcriptase Polymerase Chain Reaction
Signal Transduction*
Smad Proteins, Receptor-Regulated / genetics
Smad Proteins, Receptor-Regulated / metabolism*
Transforming Growth Factor beta1 / pharmacology
|
| IF |
1.655
|
| Times Cited |
41
|
|
WOS Category
|
GENETICS & HEREDITY
CELL BIOLOGY
|
| Resource |
| Human and Animal Cells |
COS-7(RCB0539)
HeLa(RCB0007)
Hep G2
MC3T3-E1(RCB1126)
RAW 264(RCB0535) |
