RET alternate splicing influences the interaction of activated RET with the SH2 and PTB domains of Shc, and the SH2 domain of Grb2
| Autor: | Timothy J. Stonehouse, Tony Pawson, Bruce Ponder, Gerald D. Gish, Darrin P. Smith, Carol Houghton, M. J. Lorenzo |
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| Rok vydání: | 1997 |
| Předmět: |
congenital
hereditary and neonatal diseases and abnormalities Cancer Research endocrine system diseases Molecular Sequence Data Multiple Endocrine Neoplasia Type 2a macromolecular substances Transfection medicine.disease_cause SH2 domain environment and public health src Homology Domains Germline mutation Proto-Oncogene Proteins Genetics medicine Drosophila Proteins Humans Missense mutation Amino Acid Sequence Hirschsprung Disease Phosphorylation Kinase activity Molecular Biology Adaptor Proteins Signal Transducing GRB2 Adaptor Protein Mutation integumentary system biology Proto-Oncogene Proteins c-ret Alternative splicing Proteins Receptor Protein-Tyrosine Kinases Enzyme Activation Alternative Splicing biology.protein Cancer research GRB2 Phosphotyrosine-binding domain |
| Zdroj: | Oncogene. 14:763-771 |
| ISSN: | 1476-5594 0950-9232 |
| DOI: | 10.1038/sj.onc.1200894 |
| Popis: | Activating germline mutations of the RET receptor tyrosine kinase are found in the majority of cases of inherited cancer syndrome MEN 2, and inactivating mutations in some cases of dominantly inherited Hirschsprung disease. Using RET activated by a MEN 2 mutation, we show that both the SH2 and PTB domains of the adaptor protein Shc interact with RET, and we identify the PTB domain interaction site. Interaction with both the SH2 and PTB domains of Shc contributes to the transcriptional activation of a serum response element. RET alternate splicing affects the strength of interaction with both the Shc SH2 and PTB domains. In addition, a splice isoform-specific HSCR missense mutation, which does not inactivate the RET kinase activity, decreases the strength of the PTB domain interaction and the level of RET-dependent Shc phosphorylation. |
| Databáze: | OpenAIRE |
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