MAP kinase subcellular localization controls both pattern and proliferation in the developing Drosophila wing.
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.
Marenda
Daniel R
DR
Department of Cell Biology, Emory University School of Medicine, Atlanta, GA 30322, USA.
Vrailas
Alysia D
AD
Rodrigues
Aloma B
AB
Cook
Summer
S
Powers
Maureen A
MA
Lorenzen
James A
JA
Perkins
Lizabeth A
LA
Moses
Kevin
K
D000818:Animals; D002454:Cell Differentiation / Q000502:physiology*; D002467:Cell Nucleus / Q000378:metabolism; D049109:Cell Proliferation; D003593:Cytoplasm / Q000378:metabolism*; D004330:Drosophila; D005434:Flow Cytometry; D018840:HSP70 Heat-Shock Proteins / Q000378:metabolism; D006358:Hot Temperature; D007150:Immunohistochemistry; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism*; D010766:Phosphorylation; D021381:Protein Transport / Q000502:physiology; D015398:Signal Transduction / Q000502:physiology*; D014921:Wings, Animal / Q000201:enzymology / Q000254:growth & development*
D018840:HSP70 Heat-Shock Proteins; D020928:Mitogen-Activated Protein Kinases