MAP kinase phosphorylation is dispensable for cell division, but required for cell growth in Drosophila

Abstract

Proper activation of the Ras/MAPK pathway is broadly required during development, and in many cases, signal transduction downstream of the receptor is linear. Thus, different mechanisms exist to properly regulate the large number of specific developmental outputs that are required by the activation of this pathway. Previously, we have reported a regulated cytoplasmic sequestration of phosphorylated MAPK (pMAPK) in developing Drosophila compound eyes and wings “called MAPK Cytoplasmic Hold”. In the developing wing, we have shown that cytoplasmic hold promotes the differentiation of wing vein tissue, while pMAPK nuclear translocation regulates growth and division. We had also suggested that the Ras pathway signals for inducing cell growth and cell division split upstream of the nuclear translocation of MAPK itself. Here, we further refine the role of MAPK in Drosophila. We report evidence that suggests, for the first time, that the phosphorylation of MAPK is itself another step in the regulation of cell growth and division in both Drosophila wing and eye cells. We show that inhibition of MAPK phosphorylation, or pMAPK nuclear translocation, is sufficient to block cell growth, but not cell division. These data suggest that non-phosphorylated MAPK is sufficient to induce cell division, but not cell growth, once inside the nucleus of the cell.

The ERK activator, BCI, inhibits ciliogenesis and causes defects in motor behavior, ciliary gating, and cytoskeletal rearrangement

“…As shown in Fig 1F, the double ortholog mutants mkp2 × mkp3 and mkp3 × mkp5 do not respond to BCI with an increase in pMAPK expression unlike mkp2 × mkp5 and the ortholog single mutants. It has previously been shown that although pMAPK is not necessary for cell division in Drosophila, it is required for cell growth (Majumdar et al, 2010). Without this signal being generated, these cells may be stuck in cell division, which does not allow for ciliogenesis.…”