PMID- 10586060
OWN - NLM
STAT- MEDLINE
DCOM- 20000106
LR  - 20161124
IS  - 0022-1767 (Print)
IS  - 0022-1767 (Linking)
VI  - 163
IP  - 12
DP  - 1999 Dec 15
TI  - Contributions of leukemia inhibitory factor receptor and oncostatin M receptor to
      signal transduction in heterodimeric complexes with glycoprotein 130.
PG  - 6651-8
AB  - Leukemia inhibitory factor (LIF), cardiotrophin-1, ciliary neurotrophic factor,
      and oncostatin M (OSM) lead to heterodimerization of LIF receptor (LIFR) or the
      OSM-specific receptor (OSMR) with glycoprotein (gp) 130, the common receptor
      subunit for IL-6-type cytokines. Thereby intracellular signaling via Janus
      kinases (Jaks) and STAT transcription factors is initiated. We investigated the
      contributions of LIFR and OSMR to signal transduction in the context of
      heterodimers with gp130. Chimeric receptors based on the extracellular parts of
      the IL-5R alpha- and beta-chains were generated, allowing the induced
      heterodimerization of two different cytoplasmic tails. Our studies demonstrate
      that upon heterodimerization with the gp130 cytoplasmic region, the cytoplasmic
      parts of both LIFR and OSMR were critical for activation of an acute phase
      protein promoter in HepG2 hepatoma cells. The membrane-proximal region of LIFR or
      OSMR was crucial for the ability of such receptor complexes to induce DNA binding
      of STAT1 and STAT3 in COS-7 cells. Membrane-distal regions of LIFR and OSMR
      contributed to STAT activation even in the absence of gp130 STAT recruitment
      sites. We further show that the Janus kinases Jak1 and Jak2 constitutively
      associated with receptor constructs containing the cytoplasmic part of LIFR,
      OSMR, or gp130, respectively. Homodimers of the LIFR or OSMR cytoplasmic regions 
      did not elicit responses in COS-7 cells but did in HepG2 cells and in MCF-7
      breast carcinoma cells. Thus, in spite of extensive functional similarities,
      differential signaling abilities of gp130, LIFR, and OSMR may become evident in a
      cell-type-specific manner.
FAU - Hermanns, H M
AU  - Hermanns HM
AD  - Department of Biochemistry, Rheinisch-Westfalische Technische Hochschule Aachen, 
      Germany.
FAU - Radtke, S
AU  - Radtke S
FAU - Haan, C
AU  - Haan C
FAU - Schmitz-Van de Leur, H
AU  - Schmitz-Van de Leur H
FAU - Tavernier, J
AU  - Tavernier J
FAU - Heinrich, P C
AU  - Heinrich PC
FAU - Behrmann, I
AU  - Behrmann I
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - J Immunol
JT  - Journal of immunology (Baltimore, Md. : 1950)
JID - 2985117R
RN  - 0 (Antigens, CD)
RN  - 0 (DNA-Binding Proteins)
RN  - 0 (Growth Inhibitors)
RN  - 0 (IL6ST protein, human)
RN  - 0 (Interleukin-6)
RN  - 0 (LIF protein, human)
RN  - 0 (LIFR protein, human)
RN  - 0 (Leukemia Inhibitory Factor)
RN  - 0 (Leukemia Inhibitory Factor Receptor alpha Subunit)
RN  - 0 (Lymphokines)
RN  - 0 (Macromolecular Substances)
RN  - 0 (Membrane Glycoproteins)
RN  - 0 (OSM protein, human)
RN  - 0 (Peptide Fragments)
RN  - 0 (Peptides)
RN  - 0 (Proto-Oncogene Proteins)
RN  - 0 (Receptors, Cytokine)
RN  - 0 (Receptors, Interleukin)
RN  - 0 (Receptors, Interleukin-5)
RN  - 0 (Receptors, OSM-LIF)
RN  - 0 (Receptors, Oncostatin M)
RN  - 0 (STAT1 Transcription Factor)
RN  - 0 (STAT1 protein, human)
RN  - 0 (Trans-Activators)
RN  - 106956-32-5 (Oncostatin M)
RN  - 133483-10-0 (Cytokine Receptor gp130)
RN  - EC 2.7.10.1 (Protein-Tyrosine Kinases)
RN  - EC 2.7.10.2 (JAK1 protein, human)
RN  - EC 2.7.10.2 (JAK2 protein, human)
RN  - EC 2.7.10.2 (Janus Kinase 1)
RN  - EC 2.7.10.2 (Janus Kinase 2)
SB  - AIM
SB  - IM
MH  - Animals
MH  - Antigens, CD/genetics/*metabolism/physiology
MH  - COS Cells
MH  - Carcinoma, Hepatocellular
MH  - Cytokine Receptor gp130
MH  - Cytoplasm/metabolism/physiology
MH  - DNA-Binding Proteins/metabolism
MH  - Dimerization
MH  - Gene Expression Regulation/immunology
MH  - *Growth Inhibitors
MH  - Humans
MH  - *Interleukin-6
MH  - Janus Kinase 1
MH  - Janus Kinase 2
MH  - Leukemia Inhibitory Factor
MH  - Leukemia Inhibitory Factor Receptor alpha Subunit
MH  - *Lymphokines
MH  - Macromolecular Substances
MH  - Membrane Glycoproteins/genetics/*metabolism/physiology
MH  - Oncostatin M
MH  - Peptide Fragments/genetics/physiology
MH  - Peptides/genetics/metabolism
MH  - Protein-Tyrosine Kinases/metabolism
MH  - *Proto-Oncogene Proteins
MH  - Receptors, Cytokine/genetics/metabolism/*physiology
MH  - Receptors, Interleukin/metabolism
MH  - Receptors, Interleukin-5
MH  - Receptors, OSM-LIF
MH  - Receptors, Oncostatin M
MH  - STAT1 Transcription Factor
MH  - Signal Transduction/genetics/*immunology
MH  - Trans-Activators/metabolism
MH  - Tumor Cells, Cultured
EDAT- 1999/12/10 00:00
MHDA- 1999/12/10 00:01
CRDT- 1999/12/10 00:00
PHST- 1999/12/10 00:00 [pubmed]
PHST- 1999/12/10 00:01 [medline]
PHST- 1999/12/10 00:00 [entrez]
AID - ji_v163n12p6651 [pii]
PST - ppublish
SO  - J Immunol. 1999 Dec 15;163(12):6651-8.