Analysis of the neurofibromatosis type-1 (NF1) GAP-related domain by site-directed mutagenesis

Gutmann, D. H., Boguski, M., Marchuk, D., Wigler, M. H., Collins, F. S., Ballester, R. (March 1993) Analysis of the neurofibromatosis type-1 (NF1) GAP-related domain by site-directed mutagenesis. Oncogene, 8 (3). pp. 761-769. ISSN 0950-9232

URL: https://www.ncbi.nlm.nih.gov/pubmed/8437860

Abstract

The gene for von Recklinghausen neurofibromatosis type 1 (NF1) was recently identified by positional cloning and found to encode a protein with sequence similarity to a family of eucaryotic GTPase-activating proteins (GAPs). Expression of the NF1-GAP-related domain (NF1GRD) has been shown to complement yeast strains deficient in the yeast GAP homologs, IRA1 and IRA2, to interact with human RAS proteins and to accelerate the conversion of ras-GTP to ras-GDP. Further analysis of this region has revealed a number of residues that are highly conserved between members of the GAP family. Mutational analysis of a representative number of these residues produced one of three effects: (1) no change in NF1GRD function. (2) complete disruption of NF1GRD function and (3) intermediate retention of NF1GRD function. One of these mutations at residue 1423 was shown to have reduced ability to negatively regulate ras in yeast, which is interesting in tight of a recent report demonstrating a similar naturally occurring mutation in human malignancies.

Item Type: Paper
Uncontrolled Keywords: AFFINITY CAMP PHOSPHODIESTERASE affinity cAMP phosphodiesterase GTPASE-ACTIVATING PROTEIN GTPase activating protein SACCHAROMYCES-CEREVISIAE Saccharomyces cerevisiae GENE-PRODUCT Gene product RAS GTPASE GTPase MAMMALIAN GAP mammalian gap YEAST yeast IDENTIFICATION identification SEQUENCE sequence ENCODES encodes
Subjects: bioinformatics > genomics and proteomics > genetics & nucleic acid processing > protein structure, function, modification > protein types > GTPase
bioinformatics > genomics and proteomics > genetics & nucleic acid processing > DNA, RNA structure, function, modification > genes, structure and function > genes: types > RAS
bioinformatics > genomics and proteomics > genetics & nucleic acid processing > DNA, RNA structure, function, modification > genes, structure and function > gene expression
organism description > yeast
CSHL Authors:
Communities: CSHL labs > Wigler lab
Depositing User: CSHL Librarian
Date: March 1993
Date Deposited: 12 Apr 2012 18:59
Last Modified: 02 Nov 2016 16:02
URI: http://repository.cshl.edu/id/eprint/26191

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