NDR (nuclear dbf2-related) kinases represent an evolutionarily conserved subclass of AGC kinases. NDR kinases control cell morphogenesis in different organisms, ranging from yeast to mammals. Our lab previously found that Orb6 kinase regulates cell polarity by spatial control of Cdc42 GTPase (Das et al., Curr Biol. 2009 and Das et al., Science. 2012).
Our lab used an ordered fission yeast gene deletion library to perform a genome-wide screen for gene functions that display synthetic lethality or suppression interactions with an analog-sensitive Orb6 kinase mutant (orb6-as2). The potential modulators of the NDR kinase Orb6 were further refined by using computational, microscopy, mass spectrometry, and 2-hybrid analysis approaches. By this genome-wide screen, our lab has identified two genetically separable functions of Orb6, cell morphogenesis and P-body formation, mediated by two direct substrates, Gef1 (Das et al., MBoC 2015) and Sts5 (Nuñez et al., under review), respectively. Also, two other novel functions of Orb6 kinase identified from the same screens are (1) stress response and (2) autophagy regulation. Current work is focusing on the intermediate role of Orb6 kinase in connecting diverse extracellular stress signals and autophagy modulation.