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Genes & Dev. 15 (12): 1540-1553

Copyright © 2001 by Cold Spring Harbor Laboratory Press.

Vol. 15, No. 12, pp. 1540-1553, June 15, 2001

Drosophila Fos mediates ERK and JNK signals via distinct phosphorylation sites

Laura Ciapponi,1,2 David B. Jackson,1,4 Marek Mlodzik,1,3 and Dirk Bohmann1,2,5

1 European Molecular Biology Laboratory, D-69117 Heidelberg, Germany; 2 Center for Cancer Biology, Aab Institute of Biomedical Sciences, University of Rochester School of Medicine and Dentistry, Rochester, New York 14642, USA; 3 Mount Sinai School of Medicine, Department of Cell Biology and Anatomy, New York, New York 10029, USA

During Drosophila development Fos acts downstream from the JNK pathway. Here we show that it can also mediate ERK signaling in wing vein formation and photoreceptor differentiation. Drosophila JNK and ERK phosphorylate D-Fos with overlapping, but distinct, patterns. Analysis of flies expressing phosphorylation site point mutants of D-Fos revealed that the transcription factor responds differentially to JNK and ERK signals. Mutations in the phosphorylation sites for JNK interfere specifically with the biological effects of JNK activation, whereas mutations in ERK phosphorylation sites affect responses to the EGF receptor-Ras-ERK pathway. These results indicate that the distinction between ERK and JNK signals can be made at the level of D-Fos, and that different pathway-specific phosphorylated forms of the protein can elicit different responses.

[Key Words: Fos; JNK; ERK; Drosophila; signal specificity]

4 Present address: LION Bioscience AG, 69120 Heidelberg, Germany.

5 Corresponding author.

GENES & DEVELOPMENT 15:1540-1553 © 2001 by Cold Spring Harbor Laboratory Press  ISSN 0890-9369/01 $5.00

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