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 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.
Myrick
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KV
Department of Pediatrics, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA.
Dearolf
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CR
D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D002874:Chromosome Mapping; D018076:DNA, Complementary / Q000737:chemistry / Q000235:genetics; D004330:Drosophila / Q000201:enzymology / Q000235:genetics* / Q000254:growth & development; D029721:Drosophila Proteins; D004789:Enzyme Activation; D015977:Eukaryotic Initiation Factor-1; D018507:Gene Expression Regulation, Developmental; D005796:Genes / Q000235:genetics; D006434:Hemocytes / Q000166:cytology / Q000378:metabolism*; D053612:Janus Kinases; D007814:Larva / Q000201:enzymology / Q000235:genetics*; D008969:Molecular Sequence Data; D010448:Peptide Initiation Factors / Q000235:genetics*; D011505:Protein-Tyrosine Kinases / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D016415:Sequence Alignment; D017422:Sequence Analysis, DNA; D017386:Sequence Homology, Amino Acid; D014157:Transcription Factors; D014158:Transcription, Genetic
D018076:DNA, Complementary; D029721:Drosophila Proteins; D015977:Eukaryotic Initiation Factor-1; D010448:Peptide Initiation Factors; D012333:RNA, Messenger; D014157:Transcription Factors; C026022:eukaryotic peptide initiation factor-1A; D011505:Protein-Tyrosine Kinases; D053612:Janus Kinases; C085845:hop protein, Drosophila