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Janus kinase (JAK)-signal transducer and activators of transcription (STAT) signaling pathways play crucial roles in lymphopoiesis. In particular, JAK3 has unique functions in the lymphoid system such that JAK3 ablation results in phenotypes resembling severe combined immunodeficiency syndrome. This review focuses on the biochemistry, immunological functions, and clinical significance of JAK3. Compared with other members of the JAK family, the biochemical properties of JAK3 are relatively less well characterized and thus largely inferred from studies of JAK2. Furthermore, new findings concerning the cross-talks between Notch and JAK signaling pathways through ubiquitin-mediated protein degradation are discussed in more detail.

Janus kinase 3: the controller and the controlled