Deregulated Ras signaling in developmental disorders: new tricks for an old dog.
Ras proteins regulate cell proliferation, survival and differentiation and are constitutively activated by somatic point mutations in many cancers. Previous studies of neurofibromatosis type 1 and Noonan syndrome also implicated hyperactive Ras in developmental disorders. Recently, germline mutations in H-RAS and K-RAS and in genes encoding other molecules in the Ras-Raf-MEK-ERK cascade were shown to underlie cases of Noonan, cardio-facio-cutaneous, and Costello syndromes. These disorders share phenotypic traits that include abnormal facial features, heart defects, and impaired growth and development. Many of these germline, disease-associated mutations encode novel Ras, Raf and MEK proteins. These studies underscore a crucial role of Ras signaling in human development.
Schubbert
Suzanne
S
Department of Pediatrics, University of California, 513 Parnassus Avenue, Room HSE-302, San Francisco, CA 94143, USA.
Bollag
Gideon
G
Shannon
Kevin
K
D018095:Germ-Line Mutation / Q000235:genetics*; D048788:Growth and Development / Q000235:genetics*; D006801:Humans; D044542:LEOPARD Syndrome / Q000235:genetics*; D008954:Models, Biological; D017253:Neurofibromatoses / Q000235:genetics*; D009634:Noonan Syndrome / Q000235:genetics*; D015398:Signal Transduction / Q000235:genetics*; D018631:ras Proteins / Q000235:genetics*
D018631:ras Proteins