Blasioli J, Paust S, Thomas M L
Howard Hughes Medical Institute, Department of Pathology and Molecular Microbiology, Center for Immunology, Washington University School of Medicine, St. Louis, Missouri 63110, USA.
J Biol Chem. 1999 Jan 22;274(4):2303-7. doi: 10.1074/jbc.274.4.2303.
CD22 phosphorylation is an early event of B cell antigen receptor engagement and results in the recruitment of the negative regulatory tyrosine phosphatase, SHP-1. Peptides representing the potential phosphorylation sites within the cytoplasmic domain of CD22 have been used to stimulate SHP-1 catalytic activity and to inhibit the binding of SHP-1 to CD22 (Doody, G., Justement, L., Delibrias, C., Matthews, R., Lin, J., Thomas, M., and Fearon, D. (1995) Science 269, 242-244). However, the sites of phosphorylation within the cytoplasmic domain of CD22 and the importance of each for the recruitment and activation of SHP-1 remain unknown. Here we demonstrate that there are multiple sites within the cytoplasmic domain of CD22 that interact with the Src homology 2 domains of SHP-1. Nevertheless, a minimum of two tyrosines in CD22 is required for the association with SHP-1. Furthermore, both Src homology 2 domains of SHP-1 are necessary for efficient binding to CD22.
CD22磷酸化是B细胞抗原受体激活的早期事件，会导致负调控酪氨酸磷酸酶SHP-1的募集。代表CD22胞质结构域内潜在磷酸化位点的肽已被用于刺激SHP-1的催化活性并抑制SHP-1与CD22的结合（杜迪，G.，贾斯特门特，L.，德利布里亚斯，C.，马修斯，R.，林，J.，托马斯，M.，费伦，D.（1995年）《科学》269卷，242 - 244页）。然而，CD22胞质结构域内的磷酸化位点以及每个位点对SHP-1募集和激活的重要性仍不清楚。在此我们证明，CD22胞质结构域内有多个位点与SHP-1的Src同源2结构域相互作用。尽管如此，CD22与SHP-1结合至少需要两个酪氨酸。此外，SHP-1的两个Src同源2结构域对于与CD22的有效结合都是必需的。
