RGD Reference Report - Somatic mutations in the neurofibromatosis 1 gene in human tumors. - Rat Genome Database

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Somatic mutations in the neurofibromatosis 1 gene in human tumors.

Authors: Li, Y  Bollag, G  Clark, R  Stevens, J  Conroy, L  Fults, D  Ward, K  Friedman, E  Samowitz, W  Robertson, M 
Citation: Li Y, etal., Cell 1992 Apr 17;69(2):275-81.
RGD ID: 1358399
Pubmed: PMID:1568247   (View Abstract at PubMed)

The neurofibromatosis 1 (NF1) gene product, neurofibromin, contains a GTPase-activating protein (GAP)-related domain, or NF1 GRD, that is able to down-regulate p21ras by stimulating its intrinsic GTPase. Since p21ras.GTP is a major regulator of growth and differentiation, mutant neurofibromins resulting from somatic mutations in the NF1 gene might interfere with ras signaling pathways and contribute to the development of tumors. We describe an amino acid substitution in the NF1 GRD, altering Lys-1423, that has occurred in three tumor types: colon adenocarcinoma, myelodysplastic syndrome, and anaplastic astrocytoma, and in one family with neurofibromatosis 1. The GAP activity of the mutant NF1 GRD is 200- to 400-fold lower than that of wild type, whereas binding affinity is unaffected. Thus, germline mutations in NF1 that cause neurofibromatosis 1 can also occur in somatic cells and contribute to the development of sporadic tumors, including tumors not associated with neurofibromatosis 1.

Objects referenced in this article
Gene Nf1 neurofibromin 1 Rattus norvegicus

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