Toll Signaling

Autophosphorylation of Pelle

Science's STKE  16 Apr 2002:
Vol. 2002, Issue 128, pp. tw138
DOI: 10.1126/stke.2002.128.tw138

Pelle is a downstream serine-threonine kinase in the Toll signaling pathway in Drosophila. Toll signaling is involved in both fly immune responses and in dorsal-ventral patterning. Shen and Manley investigated the mechanism by which Pelle is activated during Toll receptor stimulation. Pelle was phosphorylated in fly embryos at the time of Toll signaling, and flies with a gain-of-function Toll receptor exhibited enhanced Pelle phosphorylation. In transfected Schneider L2 cells, the phosphorylation status of Pelle was correlated with its ability to activate the downstream transcription factor Dorsal, and Pelle phosphorylation was enhanced by coexpression of the active mutant Toll receptor. In vitro experiments demonstrated that Pelle phosphorylation was essential for Pelle kinase activity. Autophosphorylating ability of Pelle was demonstrated by showing that phosphatase-treated Pelle preincubated with adenosine triphosphate yielded an activated Pelle. Phosphatase-treated Pelle could also phosphorylate a catalytically inactive Pelle mutant. Thus, the authors propose that Pelle exists in an inactive complex with the Toll receptor and that ligand binding induces dimerization of the complex, allowing Pelle to autophosphorylate, which then promotes the dissociation of Pelle from the complex for interaction with downstream substrates.

B. Shen, J. L. Manley, Pelle kinase is activated by autophosphorylation during Toll signaling in Drosophila. Development 129, 1925-1933 (2002). [Online Journal]