| RRC ID |
67663
|
| 著者 |
Amano Y, Ishikawa R, Sakatani T, Ichinose J, Sunohara M, Watanabe K, Kage H, Nakajima J, Nagase T, Ohishi N, Takai D.
|
| タイトル |
Oncogenic TPM3-ALK activation requires dimerization through the coiled-coil structure of TPM3.
|
| ジャーナル |
Biochem Biophys Res Commun
|
| Abstract |
Inflammatory myofibroblastic tumor (IMT) is a mesenchymal tumor that can arise from anywhere in the body. Anaplastic lymphoma kinase (ALK) gene rearrangements, most often resulting in the tropomyosin 3 (TPM3)-ALK fusion gene, are the main causes of IMT. However, the mechanism of malignant transformation in IMT has yet to be elucidated. The purpose of this study was to clarify the role of the TPM3 region in the transformation of IMT via TPM3-ALK. Lentivirus vectors containing a TPM3-ALK fusion gene lacking various lengths of TPM3 were constructed and expressed in HEK293T and NIH3T3 cell lines. Focus formation assay revealed loss of contact inhibition in NIH3T3 cells transfected with full-length TPM3-ALK, but not with ALK alone. Blue-native polyacrylamide gel electrophoresis (BN-PAGE) revealed that TPM3-ALK dimerization increased in proportion to the length of TPM3. Western blot showed phosphorylation of ALK, ERK1/2, and STAT3 in HEK293T cells transfected with TPM3-ALK. Thus, the coiled-coil structure of TPM3 contributes to the transforming ability of the TPM3-ALK fusion protein, and longer TPM3 region leads to higher dimer formation.
|
| 巻・号 |
457(3)
|
| ページ |
457-60
|
| 公開日 |
2015-2-13
|
| DOI |
10.1016/j.bbrc.2015.01.014
|
| PII |
S0006-291X(15)00036-4
|
| PMID |
25596129
|
| MeSH |
Anaplastic Lymphoma Kinase
Animals
Cell Transformation, Neoplastic / genetics
HEK293 Cells
Humans
Mice
NIH 3T3 Cells
Neoplasms, Muscle Tissue / genetics
Neoplasms, Muscle Tissue / metabolism
Oncogene Fusion
Oncogene Proteins, Fusion / chemistry
Oncogene Proteins, Fusion / genetics
Oncogene Proteins, Fusion / metabolism
Phosphorylation
Protein Interaction Domains and Motifs
Protein Multimerization
Receptor Protein-Tyrosine Kinases / chemistry*
Receptor Protein-Tyrosine Kinases / genetics
Receptor Protein-Tyrosine Kinases / metabolism*
Signal Transduction
Transfection
Tropomyosin / chemistry*
Tropomyosin / genetics
Tropomyosin / metabolism*
|
| IF |
2.985
|
| リソース情報 |
| 遺伝子材料 |
CSII-CMV-MCS-IRES2-Bsd (RDB04385) |
