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Blood, Vol. 93 No. 3 (February 1), 1999:
pp. 804-815
Reconstitution of the Functional Mouse Oncostatin M (OSM) Receptor:
Molecular Cloning of the Mouse OSM Receptor  Subunit
Minoru Tanaka,
Takahiko Hara,
Neal G. Copeland,
Debra J. Gilbert,
Nancy A. Jenkins, and
Atsushi Miyajima
From the Institute of Molecular and Cellular Biosciences, University
of Tokyo, Tokyo, Japan; and Mammalian Genetics Laboratory, Advanced
Bioscience Laboratories (ABL)-Basic Research Program,
National Cancer Institute-Frederick Cancer Research and Development
Center, Frederick, MD.
Oncostatin M (OSM) is a member of the interleukin-6 (IL-6) family of
cytokines that share the gp130 receptor subunit. Of these family
members, leukemia inhibitory factor (LIF) is most closely related to
OSM, and various overlapping biologic activities have been described
between human LIF and OSM (hLIF and hOSM). Two types of functional hOSM
receptors are known: the type I OSM receptor is identical to the LIF
receptor that consists of gp130 and the LIF receptor  subunit
(LIFR), and the type II OSM receptor consists of gp130 and the OSM
receptor subunit (OSMR). It is thus conceivable that common
biologic activities between hLIF and hOSM are mediated by the shared
type I receptor and OSM-specific activities are mediated by the type II
receptor. However, in contrast to the human receptors, recent studies
have demonstrated that mouse OSM (mOSM) does not activate the type I
receptor and exhibits unique biologic activity. To elucidate the
molecular structure of the functional mOSM receptor, we cloned a cDNA
encoding mOSMR, which is 55.5% identical to the hOSMR at the
amino acid level. mOSM-responsive cell lines express high-affinity mOSM
receptors, as well as mOSMR, whereas embryonic stem cells, which are
responsive to LIF but not to mOSM, do not express mOSMR. mOSMR
alone binds mOSM with low affinity (kd = 13.0 nmol/L)
and forms a high-affinity receptor (kd = 606 pmol/L) with gp130.
Ba/F3 transfectants expressing both mOSMR and gp130 proliferated in
response to mOSM, but failed to respond to LIF and human OSM. Thus, the
cloned mOSMR constitutes an essential and species-specific receptor
component of the functional mOSM receptor. Reminiscent of the
colocalization of the mOSM and mLIF genes, the mOSMR gene was found
to be located in the vicinity of the LIFR locus in the proximal end
of chromosome 15.
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