Reconstitution of the functional mouse oncostatin M (OSM) receptor: molecular cloning of the mouse OSM receptor beta subunit.

Reconstitution of the functional mouse oncostatin M (OSM) receptor: molecular cloning of the mouse OSM receptor beta subunit.
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功能性小鼠制瘤素 M (OSM) 受体的重建:小鼠 OSM 受体 β 亚基的分子克隆。

DOI:
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发表时间:
1999
期刊:
影响因子:
20.3
通讯作者:
Atsushi Miyajima
Atsushi Miyajima
中科院分区:
医学1区
文献类型:
--
作者:
Minoru Tanaka;Takahiko Hara;N. G. Copeland;D. J. Gilbert;Nancy A. Jenkins;Atsushi Miyajima

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肿瘤抑素M(OSM)是白介素6(IL-6)家族中的一员,与gp130受体亚基具有相同的功能。在这些家族成员中,白血病抑制因子(LIF)与OSM关系最为密切,人类LIF和OSM(hLIF和hOSM)之间存在着许多重叠的生物学活性。已知的hOSM受体有两种类型:I型OSM受体与LIF受体相同,LIF受体由gp130和LIF受体β亚基(LIFRbeta)组成;II型OSM受体由gp130和OSM受体β亚基(OSMRbeta)组成。因此可以想象,hLIF和hOSM之间的共同生物学活性是由共有的I型受体介导的,而OSM特异的活性是由II型受体介导的。然而,与人类受体不同的是,最近的研究表明,小鼠OSM(MOSM)不激活I型受体,并显示出独特的生物学活性。为了阐明功能性mOSM受体的分子结构,我们克隆了编码mOSMRbeta的cDNA,在氨基酸水平上与hOSMRbeta的同源性为55.5%。对mOSM敏感的细胞系表达高亲和力的mOSM受体和mOSMRbeta,而对LIF有反应但不对mOSM有反应的胚胎干细胞不表达mOSMRbeta。MOSMRβ单独与低亲和力的mOSM结合(kd=13.0nmol/L),并与gp130形成高亲和力的受体(kd=606pmol/L)。同时表达mOSMRbeta和gp130的BA/F3细胞对mOSM有反应,但对LIF和人OSM无反应。因此,克隆的mOSMRbeta构成了功能性mOSM受体的一个基本的和物种特异性的受体成分。与mOSM和mLIF基因共定位类似,mOSMRbeta基因被发现位于15号染色体近端LIFRbeta基因的附近。
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 beta subunit (LIFRbeta), and the type II OSM receptor consists of gp130 and the OSM receptor beta subunit (OSMRbeta). 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 mOSMRbeta, which is 55.5% identical to the hOSMRbeta at the amino acid level. mOSM-responsive cell lines express high-affinity mOSM receptors, as well as mOSMRbeta, whereas embryonic stem cells, which are responsive to LIF but not to mOSM, do not express mOSMRbeta. mOSMRbeta 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 mOSMRbeta and gp130 proliferated in response to mOSM, but failed to respond to LIF and human OSM. Thus, the cloned mOSMRbeta constitutes an essential and species-specific receptor component of the functional mOSM receptor. Reminiscent of the colocalization of the mOSM and mLIF genes, the mOSMRbeta gene was found to be located in the vicinity of the LIFRbeta locus in the proximal end of chromosome 15.
DOI: 10.1182/blood.v83.8.2023.bloodjournal8382023
发表时间: 1994-04
期刊: Blood
影响因子: 20.3
作者:
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通讯作者: Xunxiang Du;David A. Williams
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DOI: --
发表时间: 1992
期刊: Journal of immunology (Baltimore, Md. : 1950)
影响因子: --
作者:
Richards,CD;Brown,TJ;Shoyab,M;Baumann,H;Gauldie,J
通讯作者: Gauldie,J
DOI: 10.1126/science.8272873
发表时间: 1994-01-07
期刊: SCIENCE
影响因子: 56.9
作者:
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DOI: 10.1016/s1074-7613(00)80463-x
发表时间: 1998-01-01
期刊: IMMUNITY
影响因子: 32.4
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DOI: 10.1006/geno.1996.0488
发表时间: 1996-09-15
期刊: GENOMICS
影响因子: 4.4
作者:
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通讯作者: Jenkins, NA