Hyperactivation of the Drosophila Hop jak kinase causes the preferential overexpression of eIF1A transcripts in...

Jak kinase-Stat protein pathways play a critical role in the response of blood cells to a range of cytokines and growth factors. We are using the fruit fly, Drosophila melanogaster, as a model system to elucidate additional components of Jak-Stat pathways, and to determine how abnormalities in this pathway lead to hematopoietic leukemia-like defects. To identify downstream targets, we conducted a molecular screen for genes whose transcripts are overexpressed in response to activation of the Drosophila Hop Jak kinase. We identified a Drosophila homolog of eIF1A, a eukaryotic initiation factor found in humans and other eukaryotes. D-eIF1A is highly overexpressed in the hemocytes and lymph glands of third instar larvae carrying the dominant, gain-of-function mutation hop(Tum-l). A quantitative comparison of poly(A)(+) RNA levels between D-eIF1A and other known Drosophila translation initiation factors indicates that D-eIF1A transcripts preferentially overaccumulate in response to the hyperactive Hop pathway. Our results support the model that D-eIF1A is one of the target genes through which the Drosophila Jak kinase pathway regulates hemocyte development.