The mapping of the Lyn kinase binding site of the common β subunit of IL-3/granulocyte-macrophage colony-stimulating factor/IL-5 receptor

Tetsuya Adachi, Konrad Pazdrak, Susan Stafford, Rafeul Alam

    Research output: Contribution to journalArticle

    28 Citations (Scopus)

    Abstract

    It has been shown that a membrane-proximal region within common β (βc) receptor of IL-3/granulocyte-macrophage CSF/IL-5 (amino acids 450-517) is important of Lyn binding. We have shown previously that Lyn kinase is physically associated with the IL-5R βc subunit in unstimulated cells. The result suggests that this association involves binding modules that are not activation or phosphorylation dependent. The objective of this study was to map the exact Lyn binding site of βc. Using overlapping and/or sequential peptides derived from βc 450-517, we narrowed down the Lyn binding site to nine amino acid residues, βc 457-465. The P→A mutation in this region abrogated the binding to Lyn, indicating a critical role of proline residues. We created a cell-permeable Lyn-binding peptide by N-stearation. This cell- permeable peptide blocked the association of Lyn, but not Jak2 with βc in situ. We also investigated the βc binding site of Lyn kinase. Our results suggest that the N-terminal unique domain of Lyn kinase is important for binding to βc receptor. To our knowledge, this is the first molecular identification of the Lyn binding site of βc receptor. This finding may help develop specific inhibitors of Lyn-coupled signaling pathways.

    Original languageEnglish (US)
    Pages (from-to)1496-1501
    Number of pages6
    JournalJournal of Immunology
    Volume162
    Issue number3
    StatePublished - Feb 1 1999

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    Interleukin-5 Receptors
    Interleukin-3
    Granulocyte-Macrophage Colony-Stimulating Factor
    Phosphotransferases
    Binding Sites
    Peptides
    Interleukin-3 Receptors
    Amino Acids
    Interleukin-5
    Granulocytes
    Proline
    Macrophages
    Phosphorylation
    Mutation
    Membranes

    ASJC Scopus subject areas

    • Immunology

    Cite this

    The mapping of the Lyn kinase binding site of the common β subunit of IL-3/granulocyte-macrophage colony-stimulating factor/IL-5 receptor. / Adachi, Tetsuya; Pazdrak, Konrad; Stafford, Susan; Alam, Rafeul.

    In: Journal of Immunology, Vol. 162, No. 3, 01.02.1999, p. 1496-1501.

    Research output: Contribution to journalArticle

    Adachi, Tetsuya ; Pazdrak, Konrad ; Stafford, Susan ; Alam, Rafeul. / The mapping of the Lyn kinase binding site of the common β subunit of IL-3/granulocyte-macrophage colony-stimulating factor/IL-5 receptor. In: Journal of Immunology. 1999 ; Vol. 162, No. 3. pp. 1496-1501.
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