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First published online 24 November 2005
doi: 10.1242/dev.02168

Development 133, 43-51 (2006)
Published by The Company of Biologists 2006
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MAP kinase subcellular localization controls both pattern and proliferation in the developing Drosophila wing

Daniel R. Marenda1, Alysia D. Vrailas1, Aloma B. Rodrigues1, Summer Cook1, Maureen A. Powers1, James A. Lorenzen2,3, Lizabeth A. Perkins2 and Kevin Moses1,*,{dagger}

1 Department of Cell Biology, Emory University School of Medicine, Atlanta, GA 30322, USA.
2 Pediatric Surgical Research Laboratories, Massachusetts General Hospital, Harvard Medical School Boston, MA 02114, USA.
3 Department of Pediatric Gastroenterology, Medical College of Wisconsin, Milwaukee, WI 53226, USA.

{dagger} Author for correspondence (e-mail: mosesk{at}hhmi.org)

Accepted 14 October 2005

Mitogen-activated protein kinases (MAPKs) phosphorylate target proteins in both the cytoplasm and nucleus, and a strong correlation exists between the subcellular localization of MAPK and resulting cellular responses. It was thought that MAPK phosphorylation was always followed by rapid nuclear translocation. However, we and others have found that MAPK phosphorylation is not always sufficient for nuclear translocation in vivo. In the developing Drosophila wing, MAPK-mediated signaling is required both for patterning and for cell proliferation, although the mechanism of this differential control is not fully understood. Here, we show that phosphorylated MAPK (pMAPK) is held in the cytoplasm in differentiating larval and pupal wing vein cells, and we show that this cytoplasmic hold is required for vein cell fate. At the same time, we show that MAPK does move into the nucleus of other wing cells where it promotes cell proliferation. We propose a novel Ras pathway bifurcation in Drosophila and our results suggest a mechanism by which MAPK phosphorylation can signal two different cellular outcomes (differentiation versus proliferation) based on the subcellular localization of MAPK.

Key words: Drosophila, moleskin, Importin 7, Wing, MAP kinase, Cell cycle, Translocation, ERK, Ras


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