A JAK/STAT-Pdk1-S6K axis bypasses systemic growth restrictions to promote regeneration.

ABSTRACT: Inflammation triggers systemic growth restrictions, a process well characterised in tumour cachexia. Whether inflammatory tissue damage also induces growth restrictions, and how regenerating tissue overcome them, is less explored. Using a tissue damage model in Drosophila, we identify metabolic and signaling adaptations that both induce and bypass systemic growth restrictions. Expression of eiger, the Drosophila TNF-α homolog, in imaginal discs causes systemic insulin restriction and insulin resistance, reducing protein translation and proliferation in peripheral tissues. Regenerating cells overcome this by upregulating Pdk1, which is necessary and sufficient to promote protein translation via an Insulin/Akt-independent mechanism. JAK/STAT acts upstream to elevate Pdk1, defining a JAK/STAT

SUBMITTER: Vijayakumar Maya A 

PROVIDER: S-EPMC12686489 | biostudies-literature | 2025 Dec

REPOSITORIES: biostudies-literature