ESkine, a Novel β-Chemokine, Is Differentially Spliced to Produce Secretable and Nuclear Targeted Isoforms

Using the murine embryonal stem cell system, we have identified a novel gene encoding a highly divergent member of the beta-chemokine family of proinflammatory mediators and have called this protein ESkine. Much of the coding sequence for ESkine overlaps with the 3'-end of a novel interleukin 11 receptor 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 alternative stretch of amino acids that allows for nuclear targeting of this isoform. This differential splicing arises as a result of alternative 5' exon usage. These differentially spliced forms are expressed at discrete tissue loci. Thus, while ESkine is highly expressed in the placenta, PESKY is mainly 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 hemopoietic cellular populations.