Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “Leukemia Inhibitory Factor Receptor alpha Subunit”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 109 records · Page 6Linked to original sources
PubMed1999

Expression of CNTF/LIF-receptor components and activation of STAT3 signaling in axotomized facial motoneurons: evidence for a sequential postlesional function of the cytokines.

Several lines of evidence suggest that ciliary neurotrophic factor (CNTF) and leukemia inhibitory factor (LIF) are important for the survival and regeneration of axotomized motoneurons. To investigate the role of CNTF/LIF signaling in regenerative responses of motoneurons, we studied the expression of the three receptor components, CNTF receptor alpha (CNTFRalpha), LIF receptor beta (LIFRbeta), and gp130, and the activation of the STAT3 signal transduction pathway in the rat facial nucleus following peripheral nerve transection. As shown by in situ hybridization and immunoblotting, axotomy resulted in a rapid down-regulation of CNTFRalpha mRNA expression within 24 h and a concomitant massive up-regulation of LIFRbeta mRNA and protein in the lesioned motoneurons. The altered mRNA levels were maintained for 3 weeks but had returned back to control levels by 6 weeks postlesion after successful regeneration. In contrast, mRNA levels remained in the lesioned state during the 6-week period studied, when regeneration was prevented by nerve resection. Significant lesion-induced changes in gp130 mRNA levels were not detectable. Rapid (within 24 h) and sustained (for at least 5 days) activation of STAT3 in axotomized facial motoneurons was revealed by demonstrating the phosphorylation and nuclear translocation of the protein using immunocytochemistry and immunoblotting. In agreement with previous studies showing a complementary regulation of CNTF and LIF in the lesioned facial nerve, our observations on the postlesional regulation of CNTF/LIF receptor components in the facial nucleus indicate a direct and sequential action of the two neurotrophic proteins on axotomized facial motoneurons.

Acute-Phase Proteins↗
PubMed2001

Signaling pathway of ciliary neurotrophic factor in neuroblastoma cell lines.

BACKGROUND: Ciliary neurotrophic factor (CNTF) is a member of the interleukin-6 (IL-6) cytokine family and affects the survival and differentiation of several classes of neurons. For signal transduction, CNTF requires a receptor complex, composed of the IL-6 signal transducing molecule gp130, leukemia inhibitory factor receptor (LIFR)-beta, and CNTFR-alpha. There are two major independent pathways (Jak-STAT and Ras-MAPK) in cell signaling, and some recent reports show interaction between these pathways. The signal of the IL-6 family is mainly transduced to the Jak-STAT pathway through gp130. However, it has not been examined in neuroblastoma in detail. PROCEDURE AND RESULTS: Here we examine the signaling pathway of CNTF in 11 neuroblastoma cell lines. Northern blot analysis revealed that 3 of the 11 cell lines expressed c-fos mRNA after CNTF stimulation. Cell lysates were immunoprecipitated with agarose-conjugated antiphosphotyrosine antibody and blotted with anti-gp130, anti-Jak1, or anti-STAT3 antibody. Tyrosine phosphorylation of gp130, Jak1, and STAT3 was observed after CNTF stimulation in these three cell lines. Furthermore, tyrosine phosphorylation of ERK1 (one of the MAPKs) was also observed in all of them. CONCLUSIONS: These results demonstrate that CNTF signaling is conserved in some of the neuroblastoma cell lines and suggest that not only a Jak-STAT pathway but a MAPK pathway is activated by CNTF through gp130 in neuroblastoma cell lines.

Antigens, CD↗
PubMed2001

Leukemia inhibitory factor, interleukin-6, and their receptors are expressed transiently in the olfactory mucosa after target ablation.

Removal of the synaptic targets of olfactory receptor neurons by olfactory bulb ablation results in apoptosis of olfactory receptor neurons and up-regulation of proliferation of their progenitors. This study focuses on the expression of the neuropoietic cytokines leukemia inhibitory factor (LIF) and its receptor (LIFR) and interleukin 6 (IL-6) and its receptor (IL-6R) in intercellular signaling pathways in the olfactory mucosa after target ablation. Olfactory bulbectomy (OBX) resulted in several transient, early-onset, temporally integrated events that were detected immunohistochemically. Macrophages infiltrated the olfactory epithelium (OE) by 16 hours post-OBX. LIF expression was up-regulated transiently at 2 days post-OBX, when up-regulated expression of LIFR also was detected on globose basal cells (GBCs), a subpopulation of which are immediate progenitors of olfactory receptor neurons. GBC proliferation peaked at 3--4 days post-OBX. In the olfactory nerve (ON), LIF-positive and IL-6-positive macrophage infiltration was followed by the transient up-regulation of expression of LIFR, IL-6, and IL-6R in ensheathing cells by 3 days post-OBX. The mRNAs for LIF/LIFR, IL-6/IL-6R, and their common signal-transduction molecule, gp130, in olfactory-nasal mucosa from control mice and from 3-day post-OBX mice were detected with reverse transcriptase-polymerase chain reaction (RT-PCR). Analysis of Northern blot and relative quantitative RT-PCR demonstrated similar temporal patterns of changes in relative mRNA levels for both LIF and IL-6, which were up-regulated by 16 hours post-OBX and peaked at 2--3 days post-OBX. These data indicate that LIF from infiltrating macrophages acts as a mitogen for GBCs and that LIF from infiltrating macrophages and IL-6 from infiltrating macrophages and ensheathing cells act as repair factors in the ON.

Animals↗
PubMed2005

Leukemia inhibitory factor promotes oligodendrocyte survival after spinal cord injury.

Injury to the mammalian spinal cord is accompanied by a delayed, secondary wave of oligodendrocyte apoptosis that arises several days after the initial injury. A strong candidate to support oligodendrocyte survival after spinal cord injury is the pleiotropic cytokine, leukemia inhibitory factor (LIF). In vitro, LIF potentiates the differentiation and survival of oligodendrocyte precursors. LIF can also prevent oligodendrocyte apoptosis in response to either growth factor removal or cytotoxic challenge. More recently, in vivo studies have demonstrated that LIF is effective in preventing oligodendrocyte death in a mouse model of multiple sclerosis, experimental autoimmune encephalomyelitis (EAE). We therefore asked whether systemic delivery of LIF could ameliorate oligodendrocyte death in a mouse model of spinal cord injury. We have found that daily administration of LIF (25 microg/kg/day) promotes oligodendrocyte survival after spinal cord injury. Interestingly however, this effect does not appear to be mediated by a direct action of LIF on the oligodendrocyte but rather via an ancillary cell type, which results in augmented expression of another trophic factor capable of supporting oligodendrocyte survival, insulin-like growth factor 1 (IGF-1).

Animals↗
PubMed2006

Endogenous leukemia inhibitory factor production limits autoimmune demyelination and oligodendrocyte loss.

Autoimmune injury to oligodendrocytes evokes an endogenous response in the central nervous system, which initially limits the acute injury to oligodendrocytes and myelin, and subsequently promotes remyelination. The key molecular and cellular events responsible for this beneficial outcome are incompletely understood. In this article, we utilize murine autoimmune encephalomyelitis (EAE) to focus on the effect of endogenously produced leukemia inhibitory factor (LIF) upon mature oligodendrocyte survival after demyelinating injury. We show that the mRNA for LIF is markedly upregulated in the spinal cord in the context of acute inflammatory demyelination. After clinical disease onset, administration of neutralizing anti-LIF antibodies over a four day period significantly worsens disease severity in two different murine EAE models. We also show that administration of neutralizing antibodies results in reduced activation of the cognate LIF receptor components in the spinal cord. Histologically, anti-LIF antibody administration increases the extent of acute demyelination (P < 0.01) and doubles the oligodendrocyte loss already induced by EAE (P < 0.05), without altering the extent of inflammatory infiltration into the spinal cord. Although acute EAE induces a rapid, three-fold increase in the proliferation of NG2 positive oligodendrocyte progenitors (P < 0.001), this response is not diminished by antagonism of endogenous LIF. We conclude that endogenous LIF is induced in response to autoimmune demyelination in the spinal cord and protects mature oligodendrocytes from demyelinating injury and cell death, thereby resulting in attenuation of clinical disease severity.

Animals↗
PubMed1991

Leukemia inhibitory factor receptor is structurally related to the IL-6 signal transducer, gp130.

Leukemia inhibitory factor (LIF) is a cytokine with a broad range of activities that in many cases parallel those of interleukin-6 (IL-6) although LIF and IL-6 appear to be structurally unrelated. A cDNA clone encoding the human LIF receptor was isolated by expression screening of a human placental cDNA library. The LIF receptor is related to the gp130 'signal-transducing' component of the IL-6 receptor and to the G-CSF receptor, with the transmembrane and cytoplasmic regions of the LIF receptor and gp130 being most closely related. This relationship suggests a common signal transduction pathway for the two receptors and may help to explain similar biological effects of the two ligands. Murine cDNAs encoding soluble LIF receptors were isolated by cross-hybridization and share 70% amino acid sequence identity to the human sequence.

Amino Acid Sequence↗
PubMed1993

Inter-species chimeras of leukaemia inhibitory factor define a major human receptor-binding determinant.

Human leukaemia inhibitory factor (hLIF) binds to both human and mouse LIF receptors (LIF-R), while mouse LIF (mLIF) binds only to mouse LIF-R. Moreover, hLIF binds with higher affinity to the mLIF-R than does mLIF. In order to define the regions of the hLIF molecule responsible for species-specific interaction with the hLIF-R and for the unusual high-affinity binding to the mLIF-R, a series of 15 mouse/human LIF hybrids has been generated. Perhaps surprisingly, both of these properties mapped to the same region of the hLIF molecule. The predominant contribution was from residues in the loop linking the third and fourth helices, with lesser contributions from residues in the third helix and the loop connecting the second and third helices in the predicted three-dimensional structure. Since all chimeras retained full biological activity and receptor-binding activity on mouse cells, and there was little variation in the specific biological activity of the purified proteins, it can be concluded that the overall secondary and tertiary structures of each chimera were intact. This observation also implied that the primary binding sites on mLIF and hLIF for the mLIF-R were unaltered by inter-species domain swapping. Consequently, the site on the hLIF molecule that confers species-specific binding to the hLIF-R and higher affinity binding to the mLIF-R, must constitute an additional interaction site to that used by both mLIF and hLIF to bind to the mLIF-R. These studies define a maximum of 15 amino acid differences between hLIF and mLIF that are responsible for the different properties of these proteins.

Amino Acid Sequence↗
PubMed2001

Biphasic effects of leukemia inhibitory factor on osteoblastic differentiation.

Leukemia inhibitory factor (LIF) is a cytokine produced by multiple cell types including osteoblasts and which is active on bone metabolism. We have previously shown that in a bone nodule forming in vitro model of osteogenesis, the fetal rat calvaria (RC) cell model, LIF inhibits osteoblast differentiation, acting on late osteoprogenitors and/or early osteoblasts. These results are in contrast to in vivo experiments, in which LIF has been found to increase bone formation. To resolve this discrepancy, we have tested the effect of LIF on rat bone marrow (RBM) stromal cell cultures, an in vitro model encompassing earlier osteoprogenitor stages. LIF inhibited cell growth in early, proliferating RBM cultures, but increased the culture saturation density. The effect of LIF on bone nodule formation in this model was cell density dependent and biphasic. Continuous treatment with LIF reduced the number of bone nodules present in confluent, more mature cultures, and the inhibitory effect was strongest when cells were plated at higher cell density than lower. In contrast, during the early stages of RBM culture, nodule numbers were higher in LIF-treated dishes than in controls, and this effect was greater in lower density cultures. Acute LIF treatment restricted to early time points increased the final number of bone nodules formed in mature RBM cell cultures, but not in RC cell cultures. Our results indicate that LIF exerts complex, stage-specific effects on osteoprogenitor recruitment, differentiation, and bone formation, and that the effects are cell nonautonomous, in the rat bone marrow stromal cell model. J. Cell. Biochem. Suppl. 36: 63-70, 2001.

Animals↗
PubMed1991

Distribution and comparison of receptors for leukemia inhibitory factor on murine hemopoietic and hepatic cells.

Leukemia inhibitory factor (LIF) is a glycoprotein that induces the differentiation of the monocytic leukemia cell line M1 but suppresses the differentiation of totipotent embryonic stem cells. In an attempt to define the normal cellular targets for LIF, the distribution of LIF receptors within hemopoietic and hepatic tissue was analyzed by binding cells with radioiodinated LIF (125I-LIF) and subsequently carrying out autoradiography. Autoradiography demonstrated that in each hemopoietic tissue examined cells of monocyte/macrophage lineage were the primary cell type labeled with 125I-LIF. Moreover, both fetal and adult parenchymal hepatocytes displayed higher levels of labeling than either monocytes or macrophages. The number of receptors per positive cell varied from 150 for bone marrow monocytes to 2,000 for adult hepatocytes. In each case, however, binding was of high affinity, with an apparent KD of 34-100 pM, and binding was specific, since labeling was competed for by unlabeled LIF but not a range of other structurally unrelated growth and differentiation factors. It is suggested that LIF may play a role in regulating macrophage function and hepatic acute phase protein synthesis in response to infection.

Animals↗
PubMed1995

Specific binding of leukemia inhibitory factor to murine myoblasts in culture.

Leukemia inhibitory factor (LIF) is a member of the cytokine family of growth factors. It has been shown to exert a variety of actions on a diverse range of cell types, including neuronal, bone, and hemopoietic cells (Hilton, 1992, Trends Biochem. Sci., 17:72-76). In many of these cell types, studies have indicated the presence of specific receptors for LIF (Godard et al., 1982, J. Biol. Chem., 267: 3214-3222; Hilton et al., Proc. Natl. Acad. Sci. USA, 85:5971-5975; Hilton and Nicola, 1992, J. Biol. Chem., 267:10238-10247.). The mechanism by which these receptors act is believed to involve tyrosine phosphorylation and the signal transducing receptor component gp130. We have previously shown that LIF is capable of inducing both human and murine myoblasts to proliferate in culture (Austin et al., 1992, J. Neurol. Sci., 112:185-191). We now report that LIF binds specifically to receptors on the surface of myoblasts, with an equilibrium dissociation constant of 400 pM and the number of receptors per cell varies with cell density. Binding competition studies showed that LIF binding to these receptor sites was not competed for by a number of other growth factors which stimulate myoblast proliferation including basic fibroblast growth factor (bFGF), transforming growth factor-alpha (TGF alpha), insulin-like growth factor 1 (IGF-1), and interleukin-6 (IL-6). There was a time and concentration-dependent down-regulation of receptor numbers following preincubation of myoblasts with LIF. The processing of these receptors subsequent to binding, involves as a first step, internalization and degradation by the myoblast. LIF appeared to stimulate myoblast proliferation rather than cell survival.

Animals↗
PubMed2004

Retinoic acid inhibits leukemia inhibitory factor signaling pathways in mouse embryonic stem cells.

Retinoic acid (RA) induces the differentiation of murine embryonic stem (ES) cells to cell types resembling those found in the early embryo. When cultured in the presence of leukemia inhibitory factor (LIF), ES cells are maintained in an undifferentiated (self-renewing) state. Addition of RA to the culture media overrides the self-renewing effects of LIF to induce ES cell differentiation. Therefore, we hypothesized that RA-induced differentiation of ES cells may be accomplished by antagonism of LIF-induced signaling pathways. We demonstrate that RA-induced differentiation of CCE ES cells is associated with (1) downregulation of the LIF receptor (LIFR); (2) decreased tyrosine phosphorylation of signal transducer and activator of transcription 3 protein (Stat3); and (3) increased activation of extracellular regulated kinase (Erk1/2). We conclude that RA induces CCE ES cell differentiation in the presence of LIF, in part, by disrupting signaling between the LIFR/gp130 receptor and nuclear targets that are required to prevent ES cell differentiation. Our data indicate that RA-induced inhibition of LIF signaling does not involve Erk1/2-dependent actions.

Animals↗
PubMed2005

GP130/OSMR is the only LIF/IL-6 family receptor complex to promote osteoblast differentiation of calvaria progenitors.

Leukemia inhibitory factor (LIF) and its receptor (LIFR) are "twins" of Oncostatin M (OSM) and OSMR, respectively, likely having arisen through gene duplications. We compared their effects in a bone nodule-forming model of in vitro osteogenesis, rat calvaria (RC) cell cultures. Using a dominant-negative LIF mutant (hLIF-05), we showed that in RC cell cultures mouse OSM (mOSM) activates exclusively glycoprotein 130 (gp130)/OSMR. In treatments starting at early nodule formation stage, LIF, mOSM, IL-11, and IL-6 + sIL-6R inhibit bone nodule formation, that is, osteoprogenitor differentiation. Treatment with mOSM, and no other cytokine of the family, in early cultures (day 1-3 or 1-4) increases bone colony numbers. hLIF-05 also dose dependently stimulates bone nodule formation, confirming the inhibitory action of gp130/LIFR on osteogenesis. In pulse treatments at successive stages of bone nodule formation and maturation, LIF blocks osteocalcin (OCN) expression by differentiated osteoblasts, but has no effect on bone sialoprotein (BSP) expression. Mouse OSM inhibits OCN and BSP expression in preconfluent cultures with no or progressively reduced effects at later stages, reflecting the disruption of early nodules, possibly due to the strong apoptotic action of mOSM in RC cell cultures. In summary, LIFR and OSMR display differential effects on differentiation and phenotypic expression of osteogenic cells, most likely through different signal transduction pathways. In particular, gp130/OSMR is the only receptor complex of the family to stimulate osteoprogenitor differentiation in the RC cell culture model.

Animals↗
PubMed2002

Leukemia inhibitory factor mRNA expression is upregulated in macrophages and olfactory receptor neurons after target ablation.

After target ablation by olfactory bulbectomy (OBX), the murine olfactory epithelium (OE) undergoes degenerative changes leading to apoptosis of olfactory receptor neurons (ORNs) followed by regenerative changes that include proliferation of progenitor cells leading to neurogenesis and ORN replacement. Macrophages recruited to the OE after OBX are involved in both the degenerative and regenerative processes. Relative quantitative RT-PCR was used to demonstrate that within hours of OBX, mRNAs encoding three key components in the leukemia inhibitory factor (LIF) signaling pathway, including LIF, LIF receptor (LIFR), and STAT3, as well as cyclin D1, a growth factor sensor indicative of progenitor cell transformation, were upregulated. These mRNAs reached peak levels of expression on or before day 3 post-OBX, coincident with the peak time for macrophage recruitment and progenitor cell proliferation. Cells expressing LIF mRNA in the OE of mice at 3 days post-OBX, the time point at which LIF mRNA expression peaked, were identified using non-isotopic in situ hybridization. LIF mRNA was localized in infiltrating macrophages; near-adjacent sections exhibited macrophages immunoreactive for F4/80, a marker for activated macrophages, in numbers commensurate with those expressing LIF mRNA. LIF mRNA was also localized in surviving ORNs, identified by their expression of olfactory marker protein (OMP) mRNA and protein in near-adjacent sections. Our data suggest that LIF functions as a mitogen originating from recruited macrophages through an intercellular signaling pathway that stimulates proliferation of progenitor cells leading to neurogenesis and regeneration, and as an intracellular survival factor for traumatized ORNs.

Animals↗
PubMed2002

Expression of leukemia inhibitory factor receptor and gp130 in mouse uterus during early pregnancy.

Leukemia inhibitory factor (LIF) is essential for implantation of mouse embryos. The aim of this study was to assess the expression and regulation of LIF receptor (LIFR) and gp130 mRNA in mouse uterus during early pregnancy using in situ hybridization and reverse transcription-polymerase chain reaction (RT-PCR). A strong level of LIFR mRNA signal was detected in the luminal epithelium on day 5 of pregnancy. On day 6-8 of pregnancy, LIFR signal was mainly localized in the decidua. LIFR signal in the luminal epithelium of ovariectomized mouse was slightly stimulated by a combination of progesterone and estrogen. By RT-PCR, LIFR mRNA signal was detected in all of the uteri from day 1-8 of pregnancy, being at the highest level on day 5. A low level of gp130 mRNA signal was seen in the glandular epithelium on day 3 of pregnancy and reached a high level on day 4 of pregnancy. gp130 signal in the decidua appeared on day 6 of pregnancy and reached a high level on day 7 and 8 of pregnancy. After the ovariectomized mouse was treated with a combination of progesterone and estrogen, a strong gp130 signal was observed in the glandular epithelium, while no signal was detected after progesterone or estrogen treatment alone. By RT-PCR analysis, gp130 mRNA was detected in all of the uteri from day 1-8 of pregnancy, being at the highest level on day 4 of pregnancy. Additionally, a high level of LIFR and gp130 mRNA signal was detected in the decidua under artificial decidualization compared to the control uninjected horn. The co-expression of a high level of LIFR and gp130 mRNA in the decidua may play a key role during the decidualization and placentation.

Animals↗
PubMed1995

Leukemia inhibitory factor, LIF receptor, and gp130 in the mouse uterus during early pregnancy.

Leukemia inhibitory factor (LIF) has been shown to play an important role in the implantation of mouse blastocysts. The present study was designed to investigate the changes of LIF protein, LIF receptor, and gp130 in the mouse uterus during the early pregnancy. LIF protein and LIF receptor were at high levels in the mouse uterus near the time of ovulation and on day 4 of pregnancy. gp130 was highest on days 3 and 4 of pregnancy. Both LIF receptor and gp130 showed strong staining in the stroma of the day 5 uterus, at a time when LIF protein was low. The presence of LIF receptor and gp130 in the luminal epithelium on day 4 and in the stroma on day 5 may indicate the site of the high affinity LIF receptor. The coexistence of a high level of LIF protein, LIF receptor, and gp130 in the day 4 uterus is consistent with the previously observed high level of uterine LIF mRNA on the same day and the importance of LIF for the blastocyst implantation in mouse.

Animals↗
PubMed1998

LIF receptor-gp130 interaction investigated by homology modeling: implications for LIF binding.

Leukemia inhibitory factor (LIF), a member of the gp130 family of helical cytokines, is involved in the hemopoietic and neural systems. The LIF signal transducing complex contains two receptor molecules, the LIF receptor (LIFR) and gp130. The extracellular region of the LIFR is unique in that it includes three membrane-proximal fibronectin type III domains and two cytokine binding domains (CBDs) separated by an immunoglobulin-like domain. Although some mutagenesis data on LIF are available, it is not yet known which regions of LIFR or gp130 bind LIF. Nor is it known whether LIFR contacts gp130 in a manner similar to the growth hormone receptor dimer and, if so, through which of its CBDs. To attempt to elucidate these matters and to investigate the receptor complex, models of the CBDs of LIFR and the CBD of gp130 were constructed. Analyses of the electrostatic isopotential surfaces of the CBD models suggest that gp130 and the membrane-proximal CBD of LIFR hetero-dimerize and bind LIF through contacts similar to those seen in the growth hormone receptor dimer. This work further demonstrates the utility of electrostatic analyses of homology models and suggests a strategy for biochemical investigations of the LIF-receptor complex.

Amino Acid Sequence↗
PubMed1997

Presence of mRNAs encoding the soluble D-factor/LIF receptor in human choriocarcinoma cells and production of the soluble receptor.

Four different kinds of cDNAs encoding the receptor for the differentiation stimulating factor (D-factor)/leukemia inhibitory factor (LIF) were isolated from a human liver cDNA library. Three kinds of the cDNAs had different intronic sequences, which introduced a termination codon before the transmembrane domain. However, the site of insertion in human cDNAs is different from those in mouse cDNAs. Recombinant proteins produced by COS-7 cells after transfection of these cDNAs bound D-factor/LIF. mRNAs corresponding to these cDNAs are expressed by the human liver, placenta, and choriocarcinoma cell line NJG. In conditioned medium of choriocarcinoma cells, a native soluble receptor for the D-factor/LIF with a dissociation constant of 7.8 nM and a MW of 160 kDa was found.

Alternative Splicing↗
PubMed1998

A selective switch-on system for self-renewal of embryonic stem cells using chimeric cytokine receptors.

Propagation of embryonic stem (ES) cells with an undifferentiated pluripotential phenotype depends on leukemia inhibitory factor (LIF). The LIF receptor complex is composed of a heterodimer of LIF receptor alpha (LIFR alpha) and gp130. To activate LIFR signaling pathways independently from endogenous ones, we constructed chimeric receptors by linking the extracellular domain of human granulocyte-macrophage colony-stimulating factor (GM-CSF) receptor alpha or beta (hGMR alpha or beta) to the transmembrane and cytoplasmic regions of either mouse LIFR alpha or gp130. hGMR alpha-mLIFR/hGMR beta-mgp130 or hGMR alpha-mgp130/hGMR beta-mgp130, but not hGMR alpha-mLIFR/hGMR beta-mLIFR, preserved the self-renewal activity in A3 ES cells. All of these chimeric receptors were phosphorylated after hGM-CSF stimulation without phosphorylation of endogenous gp130. Phosphorylation of the signal transducer and activator of transcription 3 through chimeric receptors correlated with the undifferentiated phenotype. Therefore, these chimeric receptors prove useful to analyze mechanisms of the self-renewal of ES cells.

Animals↗