Interaction of GM-CSF and IL-3 with the common beta-chain of their receptors.
J Leukoc Biol
; 57(5): 739-46, 1995 May.
Article
en En
| MEDLINE
| ID: mdl-7759954
ABSTRACT
Human granulocyte-macrophage colony-stimulating factor (GM-CSF) and interleukin (IL-3) are cytokines active in both normal and abnormal hemopoiesis, inflammation, and immunity. Their biological activity is mediated via receptors that comprise a ligand-specific alpha chain and a beta chain that is common to the GM-CSF, IL-3, and IL-5 receptors. To understand the mechanism of action of GM-CSF and IL-3 in both normal and pathological conditions, we are seeking to define the structural elements required for ligand/receptor and receptor/receptor contact and their role in cellular activation. To this end we have identified a conserved motif in the first helix of GM-CSF, Glu21 that is critical for high affinity binding and biological activity. Charge-reversal mutagenesis of this residue generates a GM-CSF analogue that is devoid of biological activity and can antagonize the activity of wild-type GM-CSF. This probably results from the selective deficiency in interaction with the beta chain of the receptor and suggests that similar antagonists for IL-3 and IL-5 are also feasible. Complementary mutagenesis studies on the receptor beta chain have identified the putative B'-C' loop in the membrane-proximal domain as being critical for the high affinity binding of GM-CSF but not IL-3. Characterization of the specificity of sites of interaction between the ligands and receptors may permit the design of specific or genetic antagonists that may have important therapeutic implications.
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Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Factor Estimulante de Colonias de Granulocitos y Macrófagos
/
Receptores de Interleucina-3
/
Interleucina-3
/
Receptores de Factor Estimulante de Colonias de Granulocitos y Macrófagos
Tipo de estudio:
Prognostic_studies
Límite:
Humans
Idioma:
En
Revista:
J Leukoc Biol
Año:
1995
Tipo del documento:
Article