Numerous Serine/Threonine Kinases Affect Blood Cell Homeostasis in Drosophila melanogaster

Abstract

Blood cells in Drosophila serve primarily innate immune responses. Various stressors influence blood cell homeostasis regarding both numbers and the proportion of blood cell types. The principle molecular mechanisms governing hematopoiesis are conserved amongst species and involve major signaling pathways like Notch, Toll, JNK, JAK/Stat or RTK. Albeit signaling pathways generally rely on the activity of protein kinases, their specific contribution to hematopoiesis remains understudied. Here, we assess the role of Serine/Threonine kinases with the potential to phosphorylate the transcription factor Su(H) in crystal cell homeostasis. Su(H) is central to Notch signal transduction, and its inhibition by phosphorylation impedes crystal cell formation. Overall, nearly twenty percent of all Drosophila Serine/Threonine kinases were studied in two assays, global and hemocyte-specific overexpression and downregulation, respectively. Unexpectedly, the majority of kinases influenced crystal cell numbers, albeit only a few were related to hematopoiesis so far. Four kinases appeared essential for crystal cell formation, whereas most kinases restrained crystal cell development. This group comprises all kinase classes, indicative of the complex regulatory network underlying blood cell homeostasis. The rather indiscriminative response we observed opens the possibility that blood cells measure their overall phospho-status as a proxy for stress-signals, and activate an adaptive immune response accordingly.

Inhibition of the Notch signal transducer CSL by Pkc53E-mediated phosphorylation to fend off parasitic immune challenge inDrosophila

“…About a third of the kinase mutants were similar to the control, whereas mutations in four kinases impeded crystal cell development or prevented it altogether. Unexpectedly, the majority of the tested kinase mutants exhibited elevated crystal cell numbers, however to a different degree (Figure 3_Figure supplement 1, Table 4 supplement) (Deichsel et al, 2024). Nineteen kinase mutants matched closely the Su(H) S269A phenotype, making those the most promising candidates to being involved in the phosphorylation of Su(H) at S 269 .…”

“…As predicted by the above experiments, this effect was alleviated by Staurosporine. Owing to the global inhibition of kinases by Staurosporine, however, a rise in crystal cells was expected, because many kinases restrict their numbers (see Figure 3_Figure supplement 1) (Deichsel et al, 2024). In contrast, Su(H) S269A mutant larvae displayed an increased number of crystal cells which can be attributed to the fact that here, Su(H) can no longer be phosphorylated and hence, is overactive in this context.…”