A critical cytoplasmic domain of the interleukin-5 (IL-5) receptor alpha chain and its function in IL-5-mediated growth signal transduction.
Interleukin-5 (IL-5) regulates the production and function of B cells, eosinophils, and basophils. The IL-5 receptor (IL-5R) consists of two distinct membrane proteins, alpha and beta. The alpha chain (IL-5R alpha) is specific to IL-5. The beta chain is the common beta chain (beta c) of receptors for IL-3 and granulocyte-macrophage colony-stimulating factor (GM-CSF). The cytoplasmic domains of both alpha and beta chains are essential for signal transduction. In this study, we generated cDNAs of IL-5R alpha having various mutations in their cytoplasmic domains and examined the function of these mutants by expressing them in IL-3-dependent FDC-P1 cells. The membrane-proximal proline-rich sequence of the cytoplasmic domain of IL-5R alpha, which is conserved among the alpha chains of IL-5R, IL-3R, and GM-CSF receptor (GM-CSFR), was found to be essential for the IL-5-induced proliferative response, expression of nuclear proto-oncogenes such as c-jun, c-fos, and c-myc, and tyrosine phosphorylation of cellular proteins including JAK2 protein-tyrosine kinase. In addition, analysis using chimeric receptors which consist of the extracellular domain of IL-5R alpha and the cytoplasmic domain of beta c suggested that dimerization of the cytoplasmic domain of beta c may be an important step in activating the IL-5R complex and transducing intracellular growth signals.
Takaki
S
S
Department of Immunology, University of Tokyo, Japan.
Kanazawa
H
H
Shiiba
M
M
Takatsu
K
K
D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D002455:Cell Division / Q000502:physiology; D002460:Cell Line; D003593:Cytoplasm / Q000502:physiology; D017931:DNA Primers / Q000235:genetics; D015870:Gene Expression; D015848:Interleukin-5 / Q000502:physiology*; D051379:Mice; D008969:Molecular Sequence Data; D010766:Phosphorylation; D011487:Protein Conformation; D011519:Proto-Oncogenes; D018123:Receptors, Interleukin / Q000737:chemistry / Q000235:genetics* / Q000502:physiology*; D053649:Receptors, Interleukin-5; D017384:Sequence Deletion; D015398:Signal Transduction / Q000502:physiology*
D017931:DNA Primers; D015848:Interleukin-5; D018123:Receptors, Interleukin; D053649:Receptors, Interleukin-5