JAK2 and JAK1 Constitutively Associate With an Interleukin-5 (IL-5) Receptor α and βc Subunit, Respectively, and Are Activated Upon IL-5 Stimulation

• Published in: Blood 1998-04, Vol.91 (7), p.2264-2271
• Main Authors: Ogata, Norihisa, Kouro, Taku, Yamada, Atsuko, Koike, Masamichi, Hanai, Nobuo, Ishikawa, Takeru, Takatsu, Kiyoshi
• Format: Article
• Language: English
• Subjects: Biological and medical sciences; Cell receptors; Cell structures and functions; Fundamental and applied biological sciences. Psychology; Hormone receptors. Growth factor receptors. Cytokine receptors. Prostaglandin receptors; Molecular and cellular biology
• ISSN: 0006-4971; 1528-0020
• DOI: 10.1182/blood.V91.7.2264

The human interleukin-5 receptor (hIL-5R) consists of a unique α subunit (hIL-5Rα) and a common β subunit (βc) that activate two Janus kinases (JAK1 and JAK2) and a signal transducer and activator of transcription (STAT5). The precise stoichiometry of the hIL-5R subunits and the role of JAK kinases used in IL-5 signaling were investigated. We analyzed the interaction between hIL-5Rα and βc by immunoprecipitation using anti–hIL-5Rα and anti-βc monoclonal antibodies. The binding of JAK1 and JAK2 to each hIL-5R subunit was also evaluated in the hIL-5–responsive cell line, TF-h5Rα. It was observed that IL-5 stimulation induced the recruitment of βc to hIL-5Rα, although in the absence of IL-5 the subunits remain independent. In the absence of IL-5, JAK2 and JAK1 were associated with hIL-5Rα and βc, respectively. IL-5 stimulation resulted in tyrosine phosphorylation of JAK2, JAK1, βc, and STAT5. Moreover, IL-5–induced dimerization of IL-5R subunits caused JAK2 activation and βc phosphorylation even in the absence of JAK1 activation. Furthermore, tyrosine phosphorylation of JAK1 was dependent on the activation of JAK2. Detailed study of the C-terminal truncated cytoplasmic domain of hIL-5Rα revealed that the cytoplasmic stretch at position 346-387, containing the proline-rich region, is necessary for JAK2 binding. These observations suggest that activation of hIL-5Rα–associated JAK2 is indispensable for the IL-5 signaling event.