The Notch-mediated hyperplasia circuitry in Drosophila reveals a Src-JNK signaling axis.
basic_science · Level V
Where this comes from
- Record sourced from PubMed, PMID 26222204.
- Also identified by DOI 10.7554/eLife.05996 and PMC identifier 4517436.
- Licence recorded as CC BY.
- The licence permits redistribution, so the abstract is shown in full and the full text is available from the publisher.
Abstract
Notch signaling controls a wide range of cell fate decisions during development and disease via synergistic interactions with other signaling pathways. Here, through a genome-wide genetic screen in Drosophila, we uncover a highly complex Notch-dependent genetic circuitry that profoundly affects proliferation and consequently hyperplasia. We report a novel synergistic relationship between Notch and either of the non-receptor tyrosine kinases Src42A and Src64B to promote hyperplasia and tissue disorganization, which results in cell cycle perturbation, JAK/STAT signal activation, and differential regulation of Notch targets. Significantly, the JNK pathway is responsible for the majority of the phenotypes and transcriptional changes downstream of Notch-Src synergy. We previously reported that Notch-Mef2 also activates JNK, indicating that there are commonalities within the Notch-dependent proliferation circuitry; however, the current data indicate that Notch-Src accesses JNK in a significantly different fashion than Notch-Mef2.
Medical subject headings
- Cell Proliferation
- Drosophila Proteins
- Hyperplasia
- MAP Kinase Kinase 4
- MAP Kinase Signaling System
- Protein-Tyrosine Kinases
- Proto-Oncogene Proteins
- Proto-Oncogene Proteins pp60(c-src)
- Receptors, Notch