Mechanism of activation of the GM-CSF, IL-3, and IL-5 family of receptors. 1998

M A Guthridge, and F C Stomski, and D Thomas, and J M Woodcock, and C J Bagley, and M C Berndt, and A F Lopez
Division of Human Immunology, The Hanson Centre for Cancer Research, The Institute of Medical and Veterinary Science, Adelaide, SA, Australia.

The process of ligand binding leading to receptor activation is an ordered and sequential one. High-affinity binding of GM-CSF, interleukin 3 (IL-3), and IL-5 to their receptors induces a number of key events at the cell surface and within the cytoplasm that are necessary for receptor activation. These include receptor oligomerization, activation of tyrosine kinase activity, phosphorylation of the receptor, and the recruitment of SH2 (src-homology) and PTB (phosphotyrosine binding) domain proteins to the receptor. Such a sequence of events represents a recurrent theme among cytokine, growth factor, and hormone receptors; however, a number of very recent and interesting findings have identified unique features in this receptor system in terms of: A) how GM-CSF/IL-3/IL-5 bind, oligomerize, and activate their cognate receptors; B) how multiple biological responses such as proliferation, survival, and differentiation can be transduced from activated GM-CSF, IL-3, or IL-5 receptors, and C) how the presence of novel phosphotyrosine-independent signaling motifs within a specific cytoplasmic domain of betaC may be important for mediating survival and differentiation by these cytokines. This review does not attempt to be all-encompassing but rather to focus on the most recent and significant discoveries that distinguish the GM-CSF/IL-3/IL-5 receptor subfamily from other cytokine receptors.

UI MeSH Term Description Entries
D007377 Interleukin-3 A multilineage cell growth factor secreted by LYMPHOCYTES; EPITHELIAL CELLS; and ASTROCYTES which stimulates clonal proliferation and differentiation of various types of blood and tissue cells. Burst-Promoting Factor, Erythrocyte,Colony-Stimulating Factor 2 Alpha,Colony-Stimulating Factor, Mast-Cell,Colony-Stimulating Factor, Multipotential,Erythrocyte Burst-Promoting Factor,IL-3,Mast-Cell Colony-Stimulating Factor,Multipotential Colony-Stimulating Factor,P-Cell Stimulating Factor,Eosinophil-Mast Cell Growth-Factor,Hematopoietin-2,Burst Promoting Factor, Erythrocyte,Colony Stimulating Factor, Mast Cell,Colony Stimulating Factor, Multipotential,Eosinophil Mast Cell Growth Factor,Erythrocyte Burst Promoting Factor,Hematopoietin 2,Interleukin 3,Multipotential Colony Stimulating Factor,P Cell Stimulating Factor
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D000818 Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA. Animal,Metazoa,Animalia
D015848 Interleukin-5 A cytokine that promotes differentiation and activation of EOSINOPHILS. It also triggers activated B-LYMPHOCYTES to differentiate into IMMUNOGLOBULIN-secreting cells. B-Cell Growth Factor-II,Eosinophil Differentiation Factor,IL-5,T-Cell Replacing Factor,BCGF-II,Differentiation Factor, Eosinophil,IL5,T-Cell-Replacing Factor,B Cell Growth Factor II,Interleukin 5,Replacing Factor, T-Cell,T Cell Replacing Factor
D016178 Granulocyte-Macrophage Colony-Stimulating Factor An acidic glycoprotein of MW 23 kDa with internal disulfide bonds. The protein is produced in response to a number of inflammatory mediators by mesenchymal cells present in the hemopoietic environment and at peripheral sites of inflammation. GM-CSF is able to stimulate the production of neutrophilic granulocytes, macrophages, and mixed granulocyte-macrophage colonies from bone marrow cells and can stimulate the formation of eosinophil colonies from fetal liver progenitor cells. GM-CSF can also stimulate some functional activities in mature granulocytes and macrophages. CSF-GM,Colony-Stimulating Factor, Granulocyte-Macrophage,GM-CSF,Histamine-Producing Cell-Stimulating Factor,CSF-2,TC-GM-CSF,Tumor-Cell Human GM Colony-Stimulating Factor,Cell-Stimulating Factor, Histamine-Producing,Colony Stimulating Factor, Granulocyte Macrophage,Granulocyte Macrophage Colony Stimulating Factor,Histamine Producing Cell Stimulating Factor,Tumor Cell Human GM Colony Stimulating Factor
D016185 Receptors, Interleukin-3 High affinity receptors for INTERLEUKIN-3. They are found on early HEMATOPOIETIC PROGENITOR CELLS; progenitors of MYELOID CELLS; EOSINOPHILS; and BASOPHILS. Interleukin-3 receptors are formed by the dimerization of the INTERLEUKIN-3 RECEPTOR ALPHA SUBUNIT and the CYTOKINE RECEPTOR COMMON BETA SUBUNIT. IL-3 Receptors,Interleukin-3 Receptors,Receptors, IL-3,IL-3 Receptor,IL3 Receptor,IL3 Receptors,Interleukin-3 Receptor,IL 3 Receptor,IL 3 Receptors,Interleukin 3 Receptor,Interleukin 3 Receptors,Receptor, IL-3,Receptor, IL3,Receptor, Interleukin-3,Receptors, IL 3,Receptors, IL3,Receptors, Interleukin 3
D016187 Receptors, Granulocyte-Macrophage Colony-Stimulating Factor Receptors that bind and internalize the granulocyte-macrophage stimulating factor. Their MW is believed to be 84 kD. The most mature myelomonocytic cells, specifically human neutrophils, macrophages, and eosinophils, express the highest number of affinity receptors for this growth factor. Antigens, CD116,CD116 Antigens,GM-CSF Receptors,CD116 Antigen,GM-CSF Receptor,Receptor, Granulocyte-Macrophage Colony-Stimulating Factor,Receptors, GM-CSF,Antigen, CD116,GM CSF Receptor,GM CSF Receptors,Receptor, GM-CSF,Receptor, Granulocyte Macrophage Colony Stimulating Factor,Receptors, GM CSF,Receptors, Granulocyte Macrophage Colony Stimulating Factor
D053649 Receptors, Interleukin-5 Cell surface receptors that are specific for INTERLEUKIN-5. They are heterodimeric proteins consisting of the INTERLEUKIN-5 RECEPTOR ALPHA SUBUNIT and the CYTOKINE RECEPTOR COMMON BETA SUBUNIT. Signaling from interleukin-5 receptors can occur through interaction of their cytoplasmic domains with SYNTENINS. IL-5 Receptors,Il-5 Receptor,Interleukin-5 Receptors,IL5 Receptor,Interleukin 5 Receptor,Interleukin-5 Receptor,IL 5 Receptors,Il 5 Receptor,Interleukin 5 Receptors,Receptor, IL5,Receptor, Il-5,Receptor, Interleukin 5,Receptor, Interleukin-5,Receptors, IL-5,Receptors, Interleukin 5
D018123 Receptors, Interleukin Cell surface proteins that bind interleukins and trigger intracellular changes influencing the behavior of cells. Interleukin Receptors,Interleukin Receptor,Receptors, Interleukins,Interleukins Receptors,Receptor, Interleukin

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