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

Publication ,  Journal Article
Gutmann, DH; Boguski, M; Marchuk, D; Wigler, M; Collins, FS; Ballester, R
Published in: Oncogene
March 1993

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 light of a recent report demonstrating a similar naturally occurring mutation in human malignancies.

Duke Scholars

Published In

Oncogene

ISSN

0950-9232

Publication Date

March 1993

Volume

8

Issue

3

Start / End Page

761 / 769

Location

England

Related Subject Headings

  • Structure-Activity Relationship
  • Proto-Oncogene Proteins p21(ras)
  • Proteins
  • Oncology & Carcinogenesis
  • Neurofibromin 1
  • Mutagenesis, Site-Directed
  • Molecular Sequence Data
  • Guanosine Triphosphate
  • Genetic Complementation Test
  • GTP Phosphohydrolases
 

Citation

APA
Chicago
ICMJE
MLA
NLM
Gutmann, D. H., Boguski, M., Marchuk, D., Wigler, M., Collins, F. S., & Ballester, R. (1993). Analysis of the neurofibromatosis type 1 (NF1) GAP-related domain by site-directed mutagenesis. Oncogene, 8(3), 761–769.
Gutmann, D. H., M. Boguski, D. Marchuk, M. Wigler, F. S. Collins, and R. Ballester. “Analysis of the neurofibromatosis type 1 (NF1) GAP-related domain by site-directed mutagenesis.Oncogene 8, no. 3 (March 1993): 761–69.
Gutmann DH, Boguski M, Marchuk D, Wigler M, Collins FS, Ballester R. Analysis of the neurofibromatosis type 1 (NF1) GAP-related domain by site-directed mutagenesis. Oncogene. 1993 Mar;8(3):761–9.
Gutmann, D. H., et al. “Analysis of the neurofibromatosis type 1 (NF1) GAP-related domain by site-directed mutagenesis.Oncogene, vol. 8, no. 3, Mar. 1993, pp. 761–69.
Gutmann DH, Boguski M, Marchuk D, Wigler M, Collins FS, Ballester R. Analysis of the neurofibromatosis type 1 (NF1) GAP-related domain by site-directed mutagenesis. Oncogene. 1993 Mar;8(3):761–769.

Published In

Oncogene

ISSN

0950-9232

Publication Date

March 1993

Volume

8

Issue

3

Start / End Page

761 / 769

Location

England

Related Subject Headings

  • Structure-Activity Relationship
  • Proto-Oncogene Proteins p21(ras)
  • Proteins
  • Oncology & Carcinogenesis
  • Neurofibromin 1
  • Mutagenesis, Site-Directed
  • Molecular Sequence Data
  • Guanosine Triphosphate
  • Genetic Complementation Test
  • GTP Phosphohydrolases