Requirement of Drosophila NF1 for activation of adenylyl cyclase by PACAP38-like neuropeptides

Guo, H. F., The, I., Hannan, F., Bernards, A., Zhong, Y. (May 1997) Requirement of Drosophila NF1 for activation of adenylyl cyclase by PACAP38-like neuropeptides. Science, 276 (5313). pp. 795-8. ISSN 0036-8075 (Print)

DOI: 10.1126/science.276.5313.795


The human neurofibromatosis type 1 (NF1) tumor suppressor protein functions as a Ras-specific guanosine triphosphatase-activating protein, but the identity of Ras- mediated pathways modulated by NF1 remains unknown. A study of Drosophila NF1 mutants revealed that NF1 is essential for the cellular response to the neuropeptide PACAP38 (pituitary adenylyl cyclase-activating polypeptide) at the neuromuscular junction. The peptide induced a 100-fold enhancement of potassium currents by activating the Ras-Raf and adenylyl cyclase-adenosine 3',5'-monophosphate (cAMP) pathways. This response was eliminated in NF1 mutants. NF1 appears to regulate the rutabaga-encoded adenylyl cyclase rather than the Ras-Raf pathway. Moreover, the NF1 defect was rescued by the exposure of cells to pharmacological treatment that increased concentrations of cAMP.

Item Type: Paper
Uncontrolled Keywords: 8-Bromo Cyclic Adenosine Monophosphate pharmacology Adenylate Cyclase metabolism Animals Animals Genetically Modified Bucladesine pharmacology Cyclic AMP metabolism Drosophila enzymology genetics Drosophila Proteins Enzyme Activation Forskolin pharmacology Genes Insect In Vitro Insect Proteins genetics physiology Mutation Nerve Tissue Proteins Neuromuscular Junction drug effects enzymology Neuropeptides metabolism pharmacology Patch-Clamp Techniques Pituitary Adenylate Cyclase-Activating Polypeptide Potassium metabolism Receptors Pituitary Adenylate Cyclase-Activating Polypeptide Receptors Pituitary Adenylate Cyclase-Activating Polypeptide Type I Receptors Pituitary Hormone metabolism Signal Transduction ras GTPase-Activating Proteins ras Proteins metabolism
Subjects: organism description > animal > insect > Drosophila
bioinformatics > genomics and proteomics > genetics & nucleic acid processing > protein structure, function, modification > protein types > NF1
CSHL Authors:
Communities: CSHL labs > Zhong lab
Depositing User: CSHL Librarian
Date: 2 May 1997
Date Deposited: 29 Mar 2012 20:25
Last Modified: 29 Mar 2012 20:25

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