title: The βc receptor family - Structural insights and their functional implications.
abstract: Granulocyte-macrophage colony-stimulating factor (GM-CSF), interleukin-3 (IL-3) and IL-5 are members of a small family of cytokines that share a beta receptor subunit (βc). These cytokines regulate the growth, differentiation, migration and effector function activities of many hematopoietic cells in bone marrow, blood and sites of inflammation. Excessive or aberrant signaling can result in chronic inflammatory conditions and myeloid leukemias. The crystal structures of the GM-CSF ternary complex, the IL-5 binary complex and the very recent IL-3 receptor alpha subunit build upon decades of structure-function studies, giving new insights into cytokine-receptor specificity and signal transduction. Selective modulation of receptor function is now a real possibility and the structures of the βc receptor family are being used to discover novel and disease-specific therapeutics.
authors.affiliation: Australian Cancer Research Foundation Rational Drug Discovery Centre, St. Vincent's Institute of Medical Research, Fitzroy, Victoria 3065, Australia. Electronic address: sbroughton@svi.edu.au.
authors.forename: Sophie E
authors.initials: SE
authors.lastname: Broughton
authors.affiliation: Australian Cancer Research Foundation Rational Drug Discovery Centre, St. Vincent's Institute of Medical Research, Fitzroy, Victoria 3065, Australia.
authors.forename: Tracy L
authors.initials: TL
authors.lastname: Nero
authors.affiliation: Australian Cancer Research Foundation Rational Drug Discovery Centre, St. Vincent's Institute of Medical Research, Fitzroy, Victoria 3065, Australia.
authors.forename: Urmi
authors.initials: U
authors.lastname: Dhagat
authors.affiliation: The Centre for Cancer Biology, SA Pathology and the University of South Australia, Adelaide, South Australia 5000, Australia.
authors.forename: Winnie L
authors.initials: WL
authors.lastname: Kan
authors.affiliation: The Centre for Cancer Biology, SA Pathology and the University of South Australia, Adelaide, South Australia 5000, Australia.
authors.forename: Timothy R
authors.initials: TR
authors.lastname: Hercus
authors.affiliation: The Centre for Cancer Biology, SA Pathology and the University of South Australia, Adelaide, South Australia 5000, Australia.
authors.forename: Denis
authors.initials: D
authors.lastname: Tvorogov
authors.affiliation: The Centre for Cancer Biology, SA Pathology and the University of South Australia, Adelaide, South Australia 5000, Australia.
authors.forename: Angel F
authors.initials: AF
authors.lastname: Lopez
authors.affiliation: Australian Cancer Research Foundation Rational Drug Discovery Centre, St. Vincent's Institute of Medical Research, Fitzroy, Victoria 3065, Australia; Department of Biochemistry and Molecular Biology, Bio21 Molecular Science and Biotechnology Institute, University of Melbourne, Parkville, Victoria 3010, Australia.
authors.forename: Michael W
authors.initials: MW
authors.lastname: Parker
mesh_terms: D000818:Animals; D053648:Cytokine Receptor Common beta Subunit / Q000737:chemistry / Q000276:immunology; D016207:Cytokines / Q000737:chemistry / Q000276:immunology; D006801:Humans; D020836:Protein Structure, Quaternary; D015398:Signal Transduction / Q000276:immunology*; D013329:Structure-Activity Relationship
chemical_list: D053648:Cytokine Receptor Common beta Subunit; D016207:Cytokines
keywords: Beta common receptor; Granulocyte–macrophage colony stimulating factor; Inflammation; Interleukin-3; Interleukin-5