GM-CSF: receptor structure and transmembrane signaling.
Human granulocyte-macrophage colony-stimulating factor (GM-CSF) both stimulates hematopoietic precursor cells to grow as well as enhances the function of mature effector cells, such as neutrophils, eosinophils and macrophages. All of the biological actions of GM-CSF appear to be mediated via binding to a single class of high-affinity receptors present on all responsive cells. Affinity cross-linking experiments demonstrate that the same 98 kDa cross-linked species seen on other GM-CSF-responsive cells is also detected on a choriocarcinoma cell line, JAR. However, JAR cells express significantly increased numbers (10,000 sites/cell) of low-affinity (Kd approximately 1.5 nM) GM receptors. The GM-CSF receptor is a glycoprotein which binds to wheat germ agglutinin-sepharose. It is dramatically downregulated on neutrophils by phorbol esters and formyl-methionyl-leucine-phenylalanine (fMLP), but not by phosphatidylinositol-dependent phospholipase C. GM-CSF primes neutrophils for enhanced response to secondary stimuli, such as ionophore and chemotactic factors. Specifically, GM-CSF enhances 3H-arachidonic acid release, synthesis of leukotriene B4 and platelet activity factor in response to fMLP and the calcium ionophores.
DiPersio
J F
JF
Department of Medicine, UCLA Medical Center 90024.
Golde
D W
DW
Gasson
J D
JD
D002462:Cell Membrane / Q000187:drug effects; D003115:Colony-Stimulating Factors / Q000378:metabolism; D003432:Cross-Linking Reagents; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D006133:Growth Substances / Q000378:metabolism; D006801:Humans; D007975:Leukotriene B4 / Q000096:biosynthesis*; D009240:N-Formylmethionine Leucyl-Phenylalanine / Q000494:pharmacology; D009504:Neutrophils / Q000378:metabolism; D043265:Phosphatidylinositol Diacylglycerol-Lyase; D010727:Phosphoric Diester Hydrolases / Q000494:pharmacology; D010972:Platelet Activating Factor / Q000096:biosynthesis*; D011956:Receptors, Cell Surface / Q000502:physiology*; D016184:Receptors, Colony-Stimulating Factor; D012685:Sepharose / Q000031:analogs & derivatives; D015398:Signal Transduction; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D014407:Tumor Cells, Cultured
D003115:Colony-Stimulating Factors; D003432:Cross-Linking Reagents; D006133:Growth Substances; D010972:Platelet Activating Factor; D011956:Receptors, Cell Surface; D016184:Receptors, Colony-Stimulating Factor; C042758:wheat germ agglutinin-sepharose 6MB; D007975:Leukotriene B4; D009240:N-Formylmethionine Leucyl-Phenylalanine; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D012685:Sepharose; D010727:Phosphoric Diester Hydrolases; D043265:Phosphatidylinositol Diacylglycerol-Lyase; D013755:Tetradecanoylphorbol Acetate