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 language||English (US)|
|Number of pages||6|
|Journal||Journal of Immunology|
|State||Published - Feb 1 1999|
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