Aberrant Regulation Of Ras Proteins In Malignant-tumor Cells From Type-1 Neurofibromatosis Patients
dc.contributor.author | Basu, T. N. | en_US |
dc.contributor.author | Gutmann, D. H. | en_US |
dc.contributor.author | Fletcher, J. A. | en_US |
dc.contributor.author | Glover, Thomas W. | en_US |
dc.contributor.author | Collins, Francis S. | en_US |
dc.contributor.author | Downward, J. | en_US |
dc.date.accessioned | 2009-06-01T17:30:08Z | |
dc.date.available | 2009-06-01T17:30:08Z | |
dc.date.issued | 1992-04-23 | en_US |
dc.identifier.citation | Basu, TN; Gutmann, DH; Fletcher, JA; Glover, TW; Collins, FS; Downward, J. (1992) "Aberrant Regulation Of Ras Proteins In Malignant-tumor Cells From Type-1 Neurofibromatosis Patients." Nature 356(6371): 713-715. <http://hdl.handle.net/2027.42/62664> | en_US |
dc.identifier.issn | 0028-0836 | en_US |
dc.identifier.uri | https://hdl.handle.net/2027.42/62664 | |
dc.identifier.uri | http://www.ncbi.nlm.nih.gov/sites/entrez?cmd=retrieve&db=pubmed&list_uids=1570015&dopt=citation | en_US |
dc.description.abstract | DEFECTS in the NF1 gene have been implicated in the inherited disorder neurofibromatosis type 1, which is characterized by several developmental abnormalities including an increased frequency of benign and malignant tumours of neural crest origin (neurofibromas and neurofibrosarcomas respectively) 1. The NF1 gene encodes a ubiquitous protein homologous to p120GAP, the GTPase-activating protein (GAP) for the products of the ras protooncogenes 2-6. When expressed in non-mammalian systems, the region of the NF1 gene homologous to p120GAP produces a protein with GAP-like activity 7-9. Here we present evidence that the ras proteins in malignant tumour cell lines from patients with type 1 neurofibromatosis are in a constitutively activated state, as judged by the guanine nucleotide bound to them, and are necessary for cellular proliferation. These cells contain p21ras and p120GAP that are both functionally wild type, but barely any functional NF1 protein. Our results show that the NF1 protein is normally essential for correct negative regulation of ras proteins in the cell, even in the presence of normal p120GAP, and they support the hypothesis that NF1 is a tumour-suppressor gene whose product acts upstream of ras. | en_US |
dc.format.extent | 576591 bytes | |
dc.format.extent | 2489 bytes | |
dc.format.mimetype | application/octet-stream | |
dc.format.mimetype | text/plain | |
dc.publisher | Macmillan Magazines Ltd. | en_US |
dc.source | Nature | en_US |
dc.title | Aberrant Regulation Of Ras Proteins In Malignant-tumor Cells From Type-1 Neurofibromatosis Patients | en_US |
dc.type | Article | en_US |
dc.subject.hlbtoplevel | Science | en_US |
dc.description.peerreviewed | Peer Reviewed | en_US |
dc.contributor.affiliationum | UNIV MICHIGAN,SCH MED,DEPT PEDIAT,ANN ARBOR,MI 48109 | en_US |
dc.contributor.affiliationum | UNIV MICHIGAN,SCH MED,DEPT HUMAN GENET,ANN ARBOR,MI 48109 | en_US |
dc.contributor.affiliationum | UNIV MICHIGAN,SCH MED,HOWARD HUGHES MED INST,ANN ARBOR,MI 48109 | en_US |
dc.contributor.affiliationum | UNIV MICHIGAN,SCH MED,DEPT INTERNAL MED,ANN ARBOR,MI 48109 | en_US |
dc.contributor.affiliationother | IMPERIAL CANC RES FUND,SIGNAL TRANSDUCT LAB,LINCOLNS INN FIELDS,LONDON WC2A 3PX,ENGLAND | en_US |
dc.contributor.affiliationother | BRIGHAM & WOMENS HOSP,DEPT PATHOL,BOSTON,MA 02115 | en_US |
dc.identifier.pmid | 1570015 | en_US |
dc.description.bitstreamurl | http://deepblue.lib.umich.edu/bitstream/2027.42/62664/1/356713a0.pdf | |
dc.identifier.doi | http://dx.doi.org/10.1038/356713a0 | en_US |
dc.identifier.source | Nature | en_US |
dc.owningcollname | Interdisciplinary and Peer-Reviewed |
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