Coupling of multicellular morphogenesis and cellular differentiation by an unusual hybrid histidine protein kinase in Myxococcus xanthus

We describe an unusual hybrid histidine protein kinase, which is important for spatially coupling cell aggregation and sporulation during fruiting body formation in Myxococcus xanthus. A rodK mutant makes abnormal fruiting bodies and spores develop outside the fruiting bodies. RodK is a soluble, cytoplasmic protein, which contains an N-terminal sensor domain, a histidine protein kinase domain and three receiver domains. In vitro phosphorylation assays showed that RodK possesses kinase activity. Kinase activity is essential for RodK function in vivo. RodK is present in vegetative cells and remains present until the late aggregation stage, after which the level decreases in a manner that depends on the intercellular A-signal. Genetic evidence suggests that RodK may regulate multiple temporally separated events during fruiting body formation including stimulation of early developmental gene expression, inhibition of A-signal production and inhibition of the intercellular C-signal transduction pathway. We speculate that RodK undergoes a change in activity during development, which is reflected in changes in phosphotransfer to the receiver domains.     

Repression of CD2 gene expression is mediated by an AP-2 related factor

Tissue specific and developmental expression of the CD2 gene is tightly regulated during T cell development. DNase I hypersensitivity analysis has revealed the presence of two sites (DHS1 and 2) located 5' to the CD2 gene which have been reported to be implicated in the developmental regulation of expression of CD2. The location of DHS2 marks the position of the minimal promoter whereas DHS1 is located approximately 1800 bp upstream. We show that repressor and derepressor activities are contained within the region of DNA marked by DHS1. The repressor is capable of regulating homologous and heterologous promoters regardless of orientation. This activity is entirely dependent upon the presence of an AP-2 binding site as mutation of this site resulted in a loss of repressor activity. A nuclear factor found in Jurkat cells specifically binds this site but was shown to be serologically distinct from AP-2.