Thymic stromal lymphopoietin (TSLP) is an interleukin-(IL)-7-like cytokine with emerging pathological importance for the development of atopic diseases such as allergic asthma bronchiale. The TSLP receptor (TSLPR), a heterodimeric type I cytokine receptor, shares the IL-7R alpha-subunit with the IL-7 receptor system. The specific TSLPR alpha-chain shows similarities with the gammac receptor chain, but has some unusual features within the receptor family in both its ligand-binding and cytoplasmic domain. The murine TSLPR signals via the signal transducers and activators of transcription STAT5 and STAT3, but is unique among cytokine receptors in that it activates STATs without the involvement of Janus (JAK) tyrosine kinases, but instead utilizes the Src type kinase Tec. Here, we show by Western blotting and reporter gene experiments in combination with the application of a specific JAK inhibitor that the human TSLP receptor, in contrast, requires the function of JAK1 and JAK2 for STAT activation. Moreover, we demonstrate that the human TSLPR mediates gene regulation not only through STAT5 and STAT3 but has also the potential to mediate transcription via STAT1. Our work should help to understand more thoroughly how TSLP triggers inflammatory responses in the course of atopic diseases.

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Small Kinetochore-Associated Protein (SKAP)/Kinastrin is a multifunctional protein with proposed roles in mitosis, apoptosis and cell migration. Exact mechanisms underlying its activities in these cellular processes are not completely understood. SKAP is predicted to have different isoforms, however, previous studies did not differentiate between them. Since distinct molecular architectures of protein isoforms often influence their localization and functions, this study aimed to examine the expression profile and functional differences between SKAP isoforms in human and mouse. Analyses of various human tissues and cells of different origin by RT-PCR, and by Western blotting and immunocytochemistry applying newly generated anti-SKAP monoclonal antibodies revealed that human SKAP exists in two protein isoforms: ubiquitously expressed SKAP16 and testis/sperm-specific SKAP1. In mouse, SKAP1 expression is detectable in testis at 4 weeks postnatally, when the first wave of spermatogenesis in mice is complete and the elongated spermatids are present in the testes. Furthermore, we identified Pontin as a new SKAP1 interaction partner. SKAP1 and Pontin co-localized in the flagellar region of human sperm suggesting a functional relevance for SKAP1-Pontin interaction in sperm motility. Since most previous studies on SKAP were performed with the testis-specific isoform SKAP1, our findings provide a new basis for future studies on the role of SKAP in both human somatic cells and male germ cells, including studies on male fertility.

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