ESkine, a novel beta-chemokine, is differentially spliced to produce secretable and nuclear targeted isoforms

Using the murine embryonal stem cell system, we have identified a novel gen e encoding a highly divergent member of the beta-chemokine family of proinf lammatory mediators and have called this protein ESkine. Much of the coding sequence for ESkine overlaps with the 3'-end of a novel interleukin 11 rec eptor alpha-like sequence on murine chromosome 4. ESkine is produced as two splice variants. One of these variants encodes a classical chemokine with an associated signal peptide, while the other variant (PESKY) possesses the main body of the chemokine but has replaced the signal peptide with an alt ernative stretch of amino acids that allows for nuclear targeting of this i soform. This differential splicing arises as a result of alternative 5' exo n usage. These differentially spliced forms are expressed at discrete tissu e loci. Thus, while ESkine is highly expressed in the placenta, PESKY is ma inly expressed in the Testes and brain and weakly in the developing embryo. Studies on the proinflammatory properties of ESkine reveal it to be active in inducing polarization of CD4(+) T cells but to be inactive on other hem opoietic cellular populations.