| 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 | Suzanne Schubbert, Gideon Bollag, Natalya Lyubynska, Hoa Nguyen, Christian P Kratz, Martin Zenker, Charlotte M Niemeyer, Anders Molven, Kevin Shannon
(Affiliation: Department of Pediatrics, University of California, 513 Parnassus Avenue, HSE 302, San Francisco, California 94143, USA.)
|
| Journal | Molecular and cellular biology
(Mol Cell Biol)
Vol. 27
Issue 22
Pg. 7765-70
(Nov 2007)
ISSN: 1098-5549 United States |
| PMID | 17875937
(Publication Type: Journal Article, Research Support, N.I.H., Extramural)
|
| Chemical References |
- Recombinant Fusion Proteins
- Guanosine Triphosphate
- ras Proteins
|
| Topics |
- Amino Acid Substitution
- Animals
- COS Cells
- Cercopithecus aethiops
- Genes, ras
- Germ Cells
(cytology, physiology)
- Guanosine Triphosphate
(metabolism)
- Humans
- Mice
- Mutation, Missense
- Noonan Syndrome
- Recombinant Fusion Proteins
(genetics, metabolism)
- Signal Transduction
(physiology)
- ras Proteins
(genetics, metabolism)
|
