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| Content Provider | Journal of Biological Chemistry (JBC) |
|---|---|
| Author | Charng, Min-Ji Zhang, Dou Kinnunen, Paı̈vi Schneider, Michael D. |
| Abstract | Transforming growth factor β (TGFβ) signal transduction is mediated by two receptor Ser/Thr kinases acting in series, type II TGFβ receptor (TβR-II) phosphorylating type I TGFβ receptor (TβR-I). Because the failure of interaction cloning, thus far, to identify bona fide TβR-I substrates might reasonably have been due to the use of inactive TβR-I as bait, we sought to identify molecules that interact specifically with active TβR-I, employing the triple mutation L193A,P194A,T204D in a yeast two-hybrid system. The Leu-Pro substitutions prevent interaction with FK506-binding protein 12 (FKBP12), whose putative function in TGFβ signaling we have previously disproved; the charge substitution at Thr204 constitutively activates TβR-I. Unlike previous screens using wild-type TβR-I, where FKBP12 predominated, none of the resulting colonies encoded FKBP12. A novel protein was identified, TβR-I-associated protein-1 (TRAP-1), that interacts in yeast specifically with mutationally activated TβR-I, but not wild-type TβR-I, TβR-II, or irrelevant proteins. In mammalian cells, TRAP-1 was co-precipitated only by mutationally activated TβR-I and ligand-activated TβR-I, but not wild-type TβR-I in the absence of TGFβ. The partial TRAP-1 protein that specifically binds these mutationally and ligand-activated forms of TβR-I can inhibit signaling by the native receptor after stimulation with TGFβ or by the constitutively activated receptor mutation, as measured by a TGFβ-dependent reporter gene. Thus, TRAP-1 can distinguish activated forms of the receptor from wild-type receptor in the absence of TGFβ and may potentially have a functional role in TGFβ signaling. |
| Related Links | http://www.jbc.org/content/273/16/9365.abstract |
| Ending Page | 9368 |
| Starting Page | 9365 |
| Page Count | 4 |
| File Format | HTM / HTML PDF |
| ISSN | 00219258 |
| Journal | Journal of Biological Chemistry (JBC) |
| Issue Number | 16 |
| Volume Number | 273 |
| DOI | 10.1074/jbc.273.16.9365 |
| e-ISSN | 1083351X |
| Language | English |
| Publisher | American Society for Biochemistry and Molecular Biology |
| Publisher Date | 1998-04-17 |
| Access Restriction | Open |
| Content Type | Text |
| Resource Type | Article |
| Subject | Cell Biology Biochemistry Molecular Biology |
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