Ret-mediated mitogenesis requires Src kinase activity
| Autor: | Melillo, R. M., Barone, M. V., Lupoli, G., Cirafici, A. M., Carlomagno, F., Visconti, R., Matoskova, B., Di Fiore, P. P., Vecchio, G., Alfredo Fusco, Santoro, M. |
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| Přispěvatelé: | Melillo, ROSA MARINA, Barone, Mv, Lupoli, G, Cirafici, Am, Carlomagno, Francesca, Visconti, R, Matoskova, B, DI FIORE, Pp, Vecchio, G, Fusco, Alfredo, Santoro, M., Carlomagno, F, Santoro, Massimo, Melillo, Rm, Barone, MARIA VITTORIA, Di Fiore, Pp, Fusco, A, Melillo, R. M., Barone, M. V., Lupoli, Gelsy, Cirafici, A. M., Carlomagno, F., Visconti, Roberta, Matoskova, B., DI FIORE, P. P., Vecchio, Giancarlo, Fusco, A. |
| Předmět: |
Glial Cell Line-Derived Neurotrophic Factor Receptors
Recombinant Fusion Proteins Cell Cycle Proto-Oncogene Proteins c-ret Receptor Protein-Tyrosine Kinases 3T3 Cells kinase activity Transfection Proto-Oncogene Mas Ret Cell Line S Phase Enzyme Activation Kinetics Mice src-Family Kinases Proto-Oncogene Proteins Proto-Oncogenes Animals Drosophila Proteins Humans Signal Transduction Src |
| Zdroj: | Scopus-Elsevier Cancer research (Chic. Ill.) 59 (1999): 1120–1126. info:cnr-pdr/source/autori:Melillo RM; Barone MV; Lupoli G; Cirafici AM; Carlomagno F; Visconti R; Matoskova B; Di Fiore PP; Vecchio G; Fusco A; Santoro M/titolo:Ret-mediated mitogenesis requires Src kinase activity/doi:/rivista:Cancer research (Chic. Ill.)/anno:1999/pagina_da:1120/pagina_a:1126/intervallo_pagine:1120–1126/volume:59 CIÊNCIAVITAE |
| Popis: | The proto-oncogene RET encodes a transmembrane growth neurotrophic receptor with tyrosine kinase (TK) activity. RET mutations are associated with several human neoplastic and nonneoplastic diseases, including thyroid papillary carcinoma, multiple endocrine neoplasia type 2 syndromes, and Hirschsprung's disease. Activation of receptor TKs results in the binding and activation of downstream signaling proteins, among which are nonreceptor TKs of the Src family. To test the involvement of c-Src in Ret-mediated signaling, we measured the levels of c-Src activity in NIH3T3 cells coexpressing Ret and the accessory GFR alpha-1 receptor or an epidermal growth factor receptor/Ret chimeric receptor when the cells were stimulated by glial cell line-derived neurotrophic factor or epidermal growth factor, respectively. Ret stimulation resulted in the activation of c-Src. We also measured the levels of Src kinase activity in cell lines expressing isoforms of the Ret receptor activated by different mutations. These cells showed higher Src kinase activity than the normal counterpart. Furthermore, we show that Ret is able to associate with the SH2 domain of Src in a phosphotyrosine-dependent fashion. Microinjection of a kinase inactive mutant of c-Src blocked Ret-mediated mitogenic effect. These experiments demonstrate that activated Ret is able to bind and stimulate c-Src kinase and that Src activation is essential for the mitogenic activity of Ret. |
| Databáze: | OpenAIRE |
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