title: Biochemical and functional characterization of germ line KRAS mutations.
abstract: Germ line missense mutations in HRAS and KRAS and in genes encoding molecules that function up- or downstream of Ras in cellular signaling networks cause a group of related developmental disorders that includes Costello syndrome, Noonan syndrome, and cardiofaciocutaneous syndrome. We performed detailed biochemical and functional studies of three mutant K-Ras proteins (P34R, D153V, and F156L) found in individuals with Noonan syndrome and cardiofaciocutaneous syndrome. Mutant K-Ras proteins demonstrate a range of gain-of-function effects in different cell types, and biochemical analysis supports the idea that the intrinsic Ras guanosine nucleotide triphosphatase (GTPase) activity, the responsiveness of these proteins to GTPase-activating proteins, and guanine nucleotide dissociation all regulate developmental programs in vivo.
authors: Department of Pediatrics, University of California, 513 Parnassus Avenue, HSE 302, San Francisco, California 94143, USA.
authors: Suzanne
authors: S
authors: Schubbert
authors: Gideon
authors: G
authors: Bollag
authors: Natalya
authors: N
authors: Lyubynska
authors: Hoa
authors: H
authors: Nguyen
authors: Christian P
authors: CP
authors: Kratz
authors: Martin
authors: M
authors: Zenker
authors: Charlotte M
authors: CM
authors: Niemeyer
authors: Anders
authors: A
authors: Molven
authors: Kevin
authors: K
authors: Shannon
mesh_terms: D019943:Amino Acid Substitution; D000818:Animals; D019556:COS Cells; D002522:Chlorocebus aethiops; D011905:Genes, ras; D005854:Germ Cells / Q000166:cytology / Q000502:physiology*; D006160:Guanosine Triphosphate / Q000378:metabolism; D006801:Humans; D051379:Mice; D020125:Mutation, Missense; D009634:Noonan Syndrome; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction / Q000502:physiology*; D018631:ras Proteins / Q000235:genetics / Q000378:metabolism
chemical_list: D011993:Recombinant Fusion Proteins; D006160:Guanosine Triphosphate; D018631:ras Proteins