Salt inducible kinases (Siks) are novel regulators of Hipk

Homeodomain-interacting protein kinase (Hipk) is an evolutionarily conserved regulator of signaling pathways, controlling growth and patterning, throughout development. Salt-inducible kinases (Siks), that conventionally function as cellular nutrient sensors, were identified in a previous screen in the lab for Hipk modifiers. Overexpression of Hipk caused tissue overgrowth due to neoplasia, that was suppressed when Siks (Sik2 or Sik3) were depleted. On the other hand, synergized tissue overgrowth was observed when Siks and Hipk were co-expressed. We also provide evidence that Siks may regulate Hipk protein levels as well as localization, and that they require their kinase function for modulating Hipk activity. Thus, our work provides a novel mechanism for upstream Hipk regulation, by Siks, also highlighting the potential cytoplasmic roles of Hipk in mediating growth.