Hyperactivation of the Drosophila Hop Jak kinase causes the preferential overexpression of eIF1A transcripts in larval blood cells

Jak kinase-Stat protein pathways play a critical role in the response of bl ood cells to a range of cytokines and growth factors. We are using the frui t fly, Drosophila melanogaster, as a model system to elucidate additional c omponents 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 o verexpressed in response to activation of the Drosophila Hop Jak kinase. We identified a Drosophila homolog of eIF1A, a eukaryotic initiation factor f ound in humans and other eukaryotes. D-eIF1A is highly overexpressed in the hemocytes and lymph glands of third instar larvae carrying the dominant, g ain-of-function mutation hop(Tum-l). A quantitative comparison of poly(A)() RNA levels between D-eIF1A and other known Drosophila translation initiat ion factors indicates that D-eIF1A transcripts preferentially overaccumulat e 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 k inase pathway regulates hemocyte development. (C) 2000 Elsevier Science B.V . All rights reserved.