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Science 2 May 1997:
Vol. 276. no. 5313, pp. 795 - 798
DOI: 10.1126/science.276.5313.795
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Reports

Requirement of Drosophila NF1 for Activation of Adenylyl Cyclase by PACAP38-Like Neuropeptides

Hui-Fu Guo, Inge The, Frances Hannan, André Bernards, Yi Zhong *

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.

H.-F. Guo, F. Hannan, Y. Zhong, Cold Spring Harbor Laboratory, 1 Bungtown Road, Cold Spring Harbor, NY 11724, USA.
I. The and A. Bernards, Massachusetts General Hospital Cancer Center, Building 149, 13th Street, Charlestown, MA 02129, USA.
*   To whom correspondence should be addressed. E-mail: zhongyi{at}cshl.org

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Science. ISSN 0036-8075 (print), 1095-9203 (online)