ABSTRACT
Homeodomain interacting protein kinase (Hipk) is a member of a novel family of serine/threonine kinases. Extensive biochemical studies of vertebrate homologs, particularly Hipk2, have identified a growing list of interactors, including proteins involved in transcriptional regulation, chromatin remodeling and essential signaling pathways such as Wnt and TGFbeta. To gain insight into the in vivo functions of the single Drosophila Hipk we characterized loss of function alleles, which revealed an essential requirement for hipk. We find that in the developing eye, hipk promotes the Notch pathway. Notch signaling acts at multiple points in eye development to promote growth, proliferation and patterning. Hipk stimulates the early function of Notch in promotion of global growth of the eye disc. It has been shown in the Drosophila eye that Hipk interferes with the repressive activity of the global co-repressor, Groucho (Gro). Here, we propose that Hipk antagonizes Gro to promote the transmission of the Notch signal, indicating that Hipk plays numerous roles in regulating gene expression through interference with the formation of Gro-containing co-repressor complexes.
Subject(s)
Basic Helix-Loop-Helix Transcription Factors/antagonists & inhibitors , Drosophila Proteins/metabolism , Drosophila melanogaster/enzymology , Eye/enzymology , Genes, Essential , Protein Kinases/metabolism , Receptors, Notch/metabolism , Repressor Proteins/antagonists & inhibitors , Signal Transduction , Amino Acid Sequence , Animals , Apoptosis , Basic Helix-Loop-Helix Transcription Factors/chemistry , Basic Helix-Loop-Helix Transcription Factors/metabolism , Cell Proliferation , Clone Cells , DNA-Binding Proteins/genetics , DNA-Binding Proteins/metabolism , Drosophila Proteins/genetics , Drosophila melanogaster/cytology , Drosophila melanogaster/growth & development , Eye/cytology , Eye/growth & development , Gene Expression Regulation, Developmental , Molecular Sequence Data , Mutation/genetics , Phenotype , Phosphorylation , Protein Binding , Protein Kinases/genetics , Repressor Proteins/chemistry , Repressor Proteins/metabolismABSTRACT
Potassium channels vary in their function and regulation, yet they maintain a number of important features - they are involved in the control of potassium flow, cell volume, cell membrane resting potential, cell excitability and hormone release. The potassium (K(+)) inward rectifier (Kir) superfamily of channels are potassium selective channels, that are sensitive to the concentration of K(+) ions. They are termed inward rectifiers since they allow a much greater K(+) influx than efflux. There are at least seven subfamilies of Kir channels, grouped according to sequence and functional similarities (Curr. Opin. Neurobiol. 5 (1995) 268; Annu. Rev. Physiol. 59 (1997) 171). While numerous Kir channels have been discovered in a variety of organisms, Drosophila inward rectifier (Dir) is the first putative inward rectifier to be studied in Drosophila. In fact, there are only three genes (including Dir) encoding putative inward rectifiers in the Drosophila genome. Though there are other known potassium channels in Drosophila such as ether-a-go-go and shaker, most are voltage-gated channels. As an important first step in characterizing Kir channels in Drosophila, we initiated studies on Dir.
