The JAK/STAT Pathway in Model Organisms

Abstract

The JAK/STAT pathway was originally identified in mammals. Studies of this pathway in the mouse have revealed that JAK/STAT signaling plays a central role during hematopoeisis and other developmental processes. The role of JAK/STAT signaling in blood appears to be conserved throughout evolution, as it is also required during fly hematopoeisis. Studies in Dictyostelium, Drosophila, and zebrafish have shown that the JAK/STAT pathway is also required in an unusually broad set of developmental decisions, including cell proliferation, cell fate determination, cell migration, planar polarity, convergent extension, and immunity. There is increasing evidence that the versatility of this pathway relies on its cooperation with other signal transduction pathways. In this review, we discuss the components of the JAK/STAT pathway in model organisms and what is known about its requirement in cellular and developmental processes. In particular, we emphasize recent insights into the role that this pathway plays in the control of cell movement.

JAK signaling globally counteracts heterochromatic gene silencing

“…Among the hop Tum-l modifiers identified, several are known to interact with the JAK/STAT pathway or to be involved in blood or tumor formation. These include the human tumor suppressor nm23-H1 homolog abnormal wing discs (awd), Toll, PIAS, NURF301 and Serrate (Ser) (Supplementary Table 1) 7,15,[21][22][23][24] , supporting the specificity of this screen.A major class of E(Tum-l) genes identified in this screen encode proteins involved in chromatin modification. These include HP1, the histone H3-K9 methyltransferase Su(var)3-9, histone deacetylase (HDAC) Rpd3 and several other chromodomain-containing proteins ( Fig.…”

“…These include HP1, the histone H3-K9 methyltransferase Su(var)3-9, histone deacetylase (HDAC) Rpd3 and several other chromodomain-containing proteins ( Fig. 1c and [3][4][5][6][7][8][9] or Rpd3 demonstrated significantly increased numbers of melanotic tumors and larval blood cells (Fig. 2a,b).…”

“…The D. melanogaster genome contains a single JAK, named Hopscotch (Hop), and a single STAT, STAT92E, that are most similar to JAK2 and STAT5, respectively [5][6][7] . Hop and STAT92E function in a canonical JAK/STAT pathway, mediating cell proliferation, differentiation and migration in a variety of developmental processes [7][8][9] .…”

“…Hop and STAT92E function in a canonical JAK/STAT pathway, mediating cell proliferation, differentiation and migration in a variety of developmental processes [7][8][9] . Tumorous-lethal (Tum-l) is an oncogenic allele of hop and encodes a hyperactive JAK kinase due to a G341E substitution [10][11][12] .…”

“…Consistently, JAK loss of function enhances heterochromatic gene silencing, whereas overexpressing HP1 suppresses oncogenic JAK-induced tumors. These results demonstrate that the JAK/STAT pathway regulates cellular epigenetic status and that globally disrupting heterochromatin-mediated tumor suppression is essential for tumorigenesis induced by JAK overactivation.The D. melanogaster genome contains a single JAK, named Hopscotch (Hop), and a single STAT, STAT92E, that are most similar to JAK2 and STAT5, respectively [5][6][7] . Hop and STAT92E function in a canonical JAK/STAT pathway, mediating cell proliferation, differentiation and migration in a variety of developmental processes [7][8][9] .…”