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JAK2 and JAK1 Constitutively Associate With an Interleukin-5 (IL-5)
Receptor  and  c Subunit, Respectively, and Are Activated Upon
IL-5 Stimulation
Norihisa Ogata,
Taku Kouro,
Atsuko Yamada,
Masamichi Koike,
Nobuo Hanai,
Takeru Ishikawa, and
Kiyoshi Takatsu
From the Department of Immunology, Institute of Medical Science,
University of Tokyo, Tokyo; Tokyo Research Institute, Kyowa-Hakko Kogyo
Co, Tokyo; and Department of Otorhinolaryngology, Kumamoto University
School of Medicine, Kumamoto, Japan.
The human interleukin-5 receptor (hIL-5R) consists of a unique  subunit (hIL-5R) and a common  subunit (c) 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-5R and c by
immunoprecipitation using anti-hIL-5R and anti-c monoclonal
antibodies. The binding of JAK1 and JAK2 to each hIL-5R subunit was
also evaluated in the hIL-5-responsive cell line, TF-h5R. It was
observed that IL-5 stimulation induced the recruitment of c to
hIL-5R, although in the absence of IL-5 the subunits remain
independent. In the absence of IL-5, JAK2 and JAK1 were associated with
hIL-5R and c, respectively. IL-5 stimulation resulted in tyrosine
phosphorylation of JAK2, JAK1, c, and STAT5. Moreover, IL-5-induced
dimerization of IL-5R subunits caused JAK2 activation and c
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-5R 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-5R-associated
JAK2 is indispensable for the IL-5 signaling event.
Blood, Vol. 91 No. 7 (April 1), 1998:
pp. 2264-2271
© 1998 by The American Society of Hematology.
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