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PAPS synthetase gene expression relates directly to the murine brachymorphism phenotype

, : PAPS synthetase gene expression relates directly to the murine brachymorphism phenotype. FASEB Journal 17(4-5): Abstract No 840 3, March

Sulfation, an important post-translational modification of numerous molecules requires the synthesis of the high-energy sulfate donor, phosphoadenosine-phosphosulfate (PAPS). In higher organisms, the synthesis of PAPS is catalyzed by a single bifunctional enzyme, PAPS synthetase (SK). We have identified a gene family encoding two SK isoforms in mouse, chick and human. Reduction of PAPS synthesis results in chondrodysplasias in mice and humans which are characterized by skeletal disorders. Mouse and chick model systems, Northern blot analysis, in situ hybridization studies, and immuno-histochemical localization using isoform specific antibodies, have demonstrated distinctly different tissue and temporal expression pattern of the two isoforms. SK1 is predominantly expressed in brain and kidney while SK2 is predominantly expressed in cartilage. These results relate directly to the chondrodystrophic phenotypes in the human and mouse SK2 mutants and indicate the SK gene family members play non-redundant roles.


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