| RRC ID |
28591
|
| 著者 |
Tsutsumi R, Masoudi M, Takahashi A, Fujii Y, Hayashi T, Kikuchi I, Satou Y, Taira M, Hatakeyama M.
|
| タイトル |
YAP and TAZ, Hippo signaling targets, act as a rheostat for nuclear SHP2 function.
|
| ジャーナル |
Dev Cell
|
| Abstract |
SHP2 is a ubiquitously expressed protein tyrosine phosphatase, deregulation of which is associated with malignant neoplasms and developmental disorders. SHP2 is required for full activation of RAS-Erk signaling in the cytoplasm and is also present in the nucleus, where it promotes Wnt target gene activation through dephosphorylation of parafibromin. SHP2 is distributed both to the cytoplasm and nucleus at low cell density but is excluded from the nucleus at high cell density. Here, we show that SHP2 physically interacts with transcriptional coactivators YAP and TAZ, targets of the cell-density-sensing Hippo signal. Through the interaction, nonphosphorylated YAP/TAZ promote nuclear translocalization of SHP2, which in turn stimulates TCF/LEF- and TEAD-regulated genes via parafibromin dephosphorylation. Conversely, YAP/TAZ phosphorylated by Hippo signaling sequester SHP2 in the cytoplasm, thereby preventing nuclear accumulation of SHP2. Hence, YAP/TAZ serve as a rheostat for nuclear SHP2 function, which is switched off by the Hippo signal.
|
| 巻・号 |
26(6)
|
| ページ |
658-65
|
| 公開日 |
2013-9-30
|
| DOI |
10.1016/j.devcel.2013.08.013
|
| PII |
S1534-5807(13)00482-6
|
| PMID |
24035415
|
| MeSH |
Active Transport, Cell Nucleus
Adaptor Proteins, Signal Transducing / metabolism*
Animals
Cell Cycle Proteins
Cell Line, Tumor
Cell Nucleus / metabolism*
Cytoplasm / metabolism
Hippo Signaling Pathway
Humans
Mice
NIH 3T3 Cells
Phosphoproteins / metabolism*
Phosphorylation
Protein Serine-Threonine Kinases / metabolism
Protein Tyrosine Phosphatase, Non-Receptor Type 11 / metabolism*
Signal Transduction
Trans-Activators
YAP-Signaling Proteins
|
| IF |
10.092
|
| 引用数 |
43
|
|
WOS 分野
|
DEVELOPMENTAL BIOLOGY
CELL BIOLOGY
|
| リソース情報 |
| 遺伝子材料 |
8xGT-IIC-LucII (RDB08067)
pcDNA3.1-pA83-HA-Yap (RDB12190)
pcDNA3.1-pA83-Lats2 (RDB12200) |
