ArticleMolecular and cellular biology1994
Functional significance of lysine 1423 of neurofibromin and characterization of a second site suppressor which rescues mutations at this residue and suppresses RAS2Val-19-activated phenotypes.
Article in Molecular and cellular biology, 1994. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
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Who cites it
15 citing papers in PubMed, 32 citations in OpenAlex.
- Inside and Out.The New England journal of medicine · 2021Article
- Clinical spectrum of individuals with pathogenic NF1 missense variants affecting p.Met1149, p.Arg1276, and p.Lys1423: genotype-phenotype study in neurofibromatosis type 1.Human mutation · 2020Article
- Computational insights of K1444N substitution in GAP-related domain of NF1 gene associated with neurofibromatosis type 1 disease: a molecular modeling and dynamics approach.Metabolic brain disease · 2018Article
- Elucidating the cancer-specific genetic alteration spectrum of glioblastoma derived cell lines from whole exome and RNA sequencing.Oncotarget · 2015Article
- Article
- The Princeton Protein Orthology Database (P-POD): a comparative genomics analysis tool for biologists.PloS one · 2007Article
- Distinct functional domains of neurofibromatosis type 1 regulate immediate versus long-term memory formation.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2007Article
- Reduced growth of Drosophila neurofibromatosis 1 mutants reflects a non-cell-autonomous requirement for GTPase-Activating Protein activity in larval neurons.Genes & development · 2006Article
- Effect of neurofibromatosis type I mutations on a novel pathway for adenylyl cyclase activation requiring neurofibromin and Ras.Human molecular genetics · 2006Article
- NF1 gene mutations represent the major molecular event underlying neurofibromatosis-Noonan syndrome.American journal of human genetics · 2005Article
- Comparison of the average structures, from molecular dynamics, of complexes of GTPase activating protein (GAP) with oncogenic and wild-type ras-p21: identification of potential effector domains.Journal of protein chemistry · 2002Article
- Structural analysis of the GAP-related domain from neurofibromin and its implications.The EMBO journal · 1998Article
- Identification of neurofibromin mutants that exhibit allele specificity or increased Ras affinity resulting in suppression of activated ras alleles.Molecular and cellular biology · 1996Article
- Molecular genetics of neurofibromatosis type 1 (NF1).Journal of medical genetics · 1996Review
- Neurofibromatosis and related tumors. Natural occurrence and animal models.The American journal of pathology · 1994Review
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Authors and funding
4 authors at 2 institutions in 1 country.
Funding
Abstract
Lysine 1423 of neurofibromin (neurofibromatosis type I gene product [NF1]) plays a crucial role in the function of NF1. Mutations of this lysine were detected in samples from a neurofibromatosis patient as well as from cancer patients. To further understand the significance of this residue, we have mutated it to all possible amino acids. Functional assays using yeast ira complementation have revealed that lysine is the only amino acid that produced functional NF1. Quantitative analyses of different mutant proteins have suggested that their GTPase-activating protein (GAP) activity is drastically reduced as a result of a decrease in their Ras affinity. Such a requirement for a specific residue is not observed in the case of other conserved residues within the GAP-related domain. We also report that another residue, phenylalanine 1434, plays an important role in NF1 function. This was first indicated by the finding that defective NF1s due to an alteration of lysine 1423 to other amino acids can be rescued by a second site intragenic mutation at residue 1434. The mutation partially restored GAP activity in the lysine mutant. When the mutation phenylalanine 1434 to serine was introduced into a wild-type NF1 protein, the resulting protein acquired the ability to suppress activated phenotypes of RAS2Val-19 cells. This suppression, however, does not involve Ras interaction, since the phenylalanine mutant does not stimulate the intrinsic GTPase activity of RAS2Val-19 protein and does not have an increased affinity for Ras proteins.
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