Rescue of a Drosophila NF1 mutant phenotype by protein kinase A.
The neurofibromatosis type 1 (NF1) tumor suppressor protein is thought to restrict cell proliferation by functioning as a Ras-specific guanosine triphosphatase-activating protein. However, Drosophila homozygous for null mutations of an NF1 homolog showed no obvious signs of perturbed Ras1-mediated signaling. Loss of NF1 resulted in a reduction in size of larvae, pupae, and adults. This size defect was not modified by manipulating Ras1 signaling but was restored by expression of activated adenosine 3', 5'-monophosphate-dependent protein kinase (PKA). Thus, NF1 and PKA appear to interact in a pathway that controls the overall growth of Drosophila.
The
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Massachusetts General Hospital Cancer Center and Harvard Medical School Building 149, 13th Street, Charlestown, MA 02129, USA.
Hannigan
G E
GE
Cowley
G S
GS
Reginald
S
S
Zhong
Y
Y
Gusella
J F
JF
Hariharan
I K
IK
Bernards
A
A
D000595:Amino Acid Sequence; D000818:Animals; D002452:Cell Count; D000242:Cyclic AMP / Q000378:metabolism; D017868:Cyclic AMP-Dependent Protein Kinases / Q000235:genetics / Q000378:metabolism*; D004330:Drosophila / Q000166:cytology / Q000235:genetics* / Q000254:growth & development / Q000378:metabolism; D029721:Drosophila Proteins; D020558:GTP Phosphohydrolases / Q000378:metabolism; D017344:Genes, Insect; D019476:Insect Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D008969:Molecular Sequence Data; D009154:Mutation; D009419:Nerve Tissue Proteins; D025542:Neurofibromin 1; D010641:Phenotype; D011506:Proteins / Q000737:chemistry / Q000235:genetics; D011993:Recombinant Fusion Proteins / Q000494:pharmacology; D015398:Signal Transduction; D020703:ras GTPase-Activating Proteins; D018631:ras Proteins / Q000378:metabolism
D029721:Drosophila Proteins; D019476:Insect Proteins; C105590:NF1 protein, Drosophila; D009419:Nerve Tissue Proteins; D025542:Neurofibromin 1; D011506:Proteins; D011993:Recombinant Fusion Proteins; D020703:ras GTPase-Activating Proteins; D000242:Cyclic AMP; D017868:Cyclic AMP-Dependent Protein Kinases; D020558:GTP Phosphohydrolases; D018631:ras Proteins