The interactions of the cytokine-binding homology region and immunoglobulin-like domains of gp130 with oncostatin M: implications for receptor complex formation.
The receptor gp130 is utilized by cytokines including interleukin 6, leukemia inhibitory factor, oncostatin M, cilary neurotrophic factor and cardiotrophin. It is essential for myocardial development and haematopoiesis during embryogenesis, and its role as a shared signal transducer among different cytokines explains their overlapping biological functions. Although gp130 contains a cytokine-binding homology region (CHR) analogous to the extracellular growth hormone receptor, the complexes that utilize gp130 are not simple dimerizations of receptors around a single cytokine but involve receptor interactions with additional sites on the ligand resulting in higher order complexes. Analysis by surface plasmon resonance of the binding of the immunoglobulin-like and CHR domains of the extracellular portion of gp130 to mutants of the cytokine oncostatin M reveal that the CHR forms the main binding site for oncostatin M by a classical site II interaction, but in addition a second interaction occurs involving the receptor's immunoglobulin-like domain and the cytokine's site III at the N-terminus of the D helix. The implications for complex formation are discussed.
Staunton
D
D
Oxford Centre for Molecular Sciences, University of Oxford, UK.
Hudson
K R
KR
Heath
J K
JK
D000595:Amino Acid Sequence; D015703:Antigens, CD / Q000737:chemistry / Q000378:metabolism*; D001483:Base Sequence; D050822:Cytokine Receptor gp130; D016207:Cytokines / Q000737:chemistry / Q000378:metabolism*; D017931:DNA Primers; D007136:Immunoglobulins / Q000378:metabolism*; D008562:Membrane Glycoproteins / Q000737:chemistry / Q000378:metabolism*; D008969:Molecular Sequence Data; D053683:Oncostatin M; D010455:Peptides / Q000302:isolation & purification / Q000378:metabolism*; D011994:Recombinant Proteins / Q000302:isolation & purification / Q000378:metabolism; D013816:Thermodynamics
D015703:Antigens, CD; D016207:Cytokines; D017931:DNA Primers; D007136:Immunoglobulins; D008562:Membrane Glycoproteins; D010455:Peptides; D011994:Recombinant Proteins; D053683:Oncostatin M; D050822:Cytokine Receptor gp130