Neurofibromin regulates G protein-stimulated adenylyl cyclase activity.
Neurofibromatosis type 1 (NF1) is a dominant genetic disorder characterized by multiple benign and malignant nervous system tumors, and by learning defects in 45% of children with NF1 mutations. Studies of neurofibromin, the protein encoded by NF1, have focused on its functions in tumorigenesis and regulation of Ras activity; however, Drosophila NF1 regulates both Ras and cyclic AMP (cAMP) pathways. Expression of a human NF1 transgene rescued cAMP-related phenotypes in NF1 mutant flies (small body size and G protein-stimulated adenylyl cyclase (AC) activity defects), and neuropeptide- and G protein-stimulated AC activity were lower in Nf1-/- as compared to Nf1+/- mouse brains, demonstrating that neurofibromin regulates AC activity in both mammals and flies.
Tong
Jiayuan
J
Cold Spring Harbor Laboratory, PO Box 100, Cold Spring Harbor, New York 11724, USA.
Hannan
Frances
F
Zhu
Yinghua
Y
Bernards
Andre
A
Zhong
Yi
Y
D000262:Adenylyl Cyclases / Q000378:metabolism*; D000818:Animals; D004330:Drosophila; D019204:GTP-Binding Proteins / Q000235:genetics / Q000502:physiology*; D016514:Genes, Neurofibromatosis 1 / Q000502:physiology; D006801:Humans; D051379:Mice; D018345:Mice, Knockout / Q000235:genetics; D009154:Mutation / Q000502:physiology; D025542:Neurofibromin 1 / Q000235:genetics / Q000502:physiology*; D019076:Transgenes / Q000502:physiology
D025542:Neurofibromin 1; D019204:GTP-Binding Proteins; D000262:Adenylyl Cyclases