Cyclin D-Cdk4 and cyclin E-Cdk2 regulate the Jak/STAT signal transduction pathway in Drosophila.
The JAK/STAT signal transduction pathway regulates many developmental processes in Drosophila. However, the functional mechanism of this pathway is poorly understood. In this report, we identify the Drosophila cyclin-dependent kinase 4 (Cdk4), which exhibits embryonic mutant phenotypes identical to those in the Hopscotch/JAK kinase and stat92E/STAT mutations. Specific genetic interactions between Cdk4 and hop mutations suggest that Cdk4 functions downstream of the HOP tyrosine kinase. We further show that Cyclin D-Cdk4 (as well as Cyclin E-Cdk2) binds and regulates STAT92E protein stability. STAT92E regulates gene expression for various biological processes, including the endocycle S phase. These data suggest that Cyclin D-Cdk4 and Cyclin E-Cdk2 play more versatile roles in Drosophila development.
Chen
Xiu
X
Laboratory of Immunobiology, National Institutes of Health, National Cancer Institute at Frederick, Frederick, MD 21702, USA.
Oh
Su-Wan
SW
Zheng
Zhiyu
Z
Chen
Hua-Wei
HW
Shin
Hyun-hee
HH
Hou
Steven X
SX
D000818:Animals; D030801:Animals, Genetically Modified; D019521:Body Patterning / Q000235:genetics*; D042846:CDC2-CDC28 Kinases; D002454:Cell Differentiation; D016764:Cell Polarity; D003433:Crosses, Genetic; D056741:Cyclin D; D019927:Cyclin E / Q000235:genetics / Q000378:metabolism*; D051357:Cyclin-Dependent Kinase 2; D051358:Cyclin-Dependent Kinase 4; D018844:Cyclin-Dependent Kinases / Q000235:genetics / Q000378:metabolism*; D016213:Cyclins / Q000235:genetics / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D029721:Drosophila Proteins / Q000378:metabolism; D004331:Drosophila melanogaster / Q000196:embryology* / Q000235:genetics; D004625:Embryo, Nonmammalian / Q000502:physiology*; D004789:Enzyme Activation; D005123:Eye / Q000166:cytology / Q000196:embryology; D005260:Female; D018507:Gene Expression Regulation, Developmental; D006023:Glycoproteins / Q000378:metabolism; D017403:In Situ Hybridization; D019476:Insect Proteins / Q000378:metabolism; D053613:Janus Kinase 1; D053612:Janus Kinases; D009154:Mutation; D009866:Oogenesis / Q000502:physiology*; D006080:Ovarian Follicle / Q000166:cytology / Q000502:physiology*; D010641:Phenotype; D017346:Protein Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism*; D011505:Protein-Tyrosine Kinases / Q000378:metabolism*; D011518:Proto-Oncogene Proteins; D050791:STAT Transcription Factors; D015398:Signal Transduction; D015534:Trans-Activators / Q000235:genetics / Q000378:metabolism*; D014157:Transcription Factors
C534694:CycD protein, Drosophila; D056741:Cyclin D; D019927:Cyclin E; D016213:Cyclins; D004268:DNA-Binding Proteins; D029721:Drosophila Proteins; D006023:Glycoproteins; D019476:Insect Proteins; D011518:Proto-Oncogene Proteins; D050791:STAT Transcription Factors; C105675:Stat92E protein, Drosophila; D015534:Trans-Activators; D014157:Transcription Factors; C115570:upd1 protein, Drosophila; D011505:Protein-Tyrosine Kinases; D053613:Janus Kinase 1; D053612:Janus Kinases; C085845:hop protein, Drosophila; D017346:Protein Serine-Threonine Kinases; D042846:CDC2-CDC28 Kinases; C495896:Cdk4 protein, Drosophila; D051357:Cyclin-Dependent Kinase 2; D051358:Cyclin-Dependent Kinase 4; D018844:Cyclin-Dependent Kinases; C495887:cdk2 protein, Drosophila