Differential shedding of transmembrane neuregulin isoforms by the tumor necrosis factor-alpha-converting enzyme
[EN]The neuregulins (NRGs) are a family of EGF-like factors that activate receptor tyrosine kinases of the ErbB/HER type. Some NRGs are membrane anchored and are released upon cleavage of the ectodomain. Here we have investigated the characteristics of the cleavage of different transmembrane NRG iso...
| Autores: | , , , , |
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| Tipo de recurso: | artículo |
| Estado: | Versión publicada |
| Fecha de publicación: | 2000 |
| País: | España |
| Institución: | Universidad de Salamanca (USAL) |
| Repositorio: | GREDOS. Repositorio Institucional de la Universidad de Salamanca |
| OAI Identifier: | oai:gredos.usal.es:10366/167789 |
| Acceso en línea: | http://hdl.handle.net/10366/167789 |
| Access Level: | acceso abierto |
| Palabra clave: | Shedding, TACE, NRG Mutagenesis Binding Sites Transfection Fibroblasts Humans Isomerism Cricetinae HeLa Cells Metalloendopeptidases Nerve Growth Factors Amino Acid Sequence Membrane Proteins Peptide Fragments Animals Protein Kinase C Alternative Splicing ADAM Proteins Protein Precursors CHO Cells Mice 2302 Bioquímica fibroblastos proteína cinasa C humanos ratones células HeLa sitios de unión transfección metaloendopeptidasas células CHO mutagénesis precursores de proteínas proteínas ADAM animales secuencia de aminoácidos isomerismo empalme alternativo proteínas de membranas fragmentos peptídicos factores de crecimiento nervioso |
| Sumario: | [EN]The neuregulins (NRGs) are a family of EGF-like factors that activate receptor tyrosine kinases of the ErbB/HER type. Some NRGs are membrane anchored and are released upon cleavage of the ectodomain. Here we have investigated the characteristics of the cleavage of different transmembrane NRG isoforms (proNRG) that diverge in domains that have been implicated in the regulation of the cleavage of other membrane-anchored growth factors. We show that cleavage of proNRGs is complex and generates several cell-bound truncated fragments. Comparison of the resting generation of these truncated fragments between proNRG forms that diverge in the linker region that connects the EGF-like module to the transmembrane domain revealed that proNRG beta 2a was relatively resistant to processing compared to proNRG beta 4a which was processed more efficiently than proNRG alpha 2a. An important role for this linker in proNRG cleavage was supported by deletion analysis of this region that prevented NRG solubilization. Studies aimed at the identification of the proteolytic machinery responsible for proNRG processing indicated that metalloproteases were involved in proNRG processing. This was further supported by the fact that cleavage of proNRG alpha 2c was defective in fibroblasts derived from TACE(-/-) animals that express an inactive form of the metalloprotease TACE. |
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