Definition of the sites of interaction between the protein tyrosine phosphatase SHP-1 and CD22.
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.
Blasioli
J
J
Howard Hughes Medical Institute, Department of Pathology and Molecular Microbiology, Center for Immunology, Washington University School of Medicine, St. Louis, Missouri 63110, USA.
Paust
S
S
Thomas
M L
ML
D000595:Amino Acid Sequence; D015703:Antigens, CD / Q000737:chemistry / Q000378:metabolism*; D000944:Antigens, Differentiation, B-Lymphocyte / Q000737:chemistry / Q000378:metabolism*; D001483:Base Sequence; D015815:Cell Adhesion Molecules; D003593:Cytoplasm / Q000378:metabolism; D017931:DNA Primers; D006367:HeLa Cells; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins; D037102:Lectins; D010766:Phosphorylation; D011485:Protein Binding; D054592:Protein Tyrosine Phosphatase, Non-Receptor Type 11; D053824:Protein Tyrosine Phosphatase, Non-Receptor Type 6; D017027:Protein Tyrosine Phosphatases / Q000378:metabolism*; D054593:SH2 Domain-Containing Protein Tyrosine Phosphatases; D051918:Sialic Acid Binding Ig-like Lectin 2; D013379:Substrate Specificity; D014443:Tyrosine / Q000378:metabolism; D018909:src Homology Domains
D015703:Antigens, CD; D000944:Antigens, Differentiation, B-Lymphocyte; C497867:CD22 protein, human; D015815:Cell Adhesion Molecules; D017931:DNA Primers; D047908:Intracellular Signaling Peptides and Proteins; D037102:Lectins; D051918:Sialic Acid Binding Ig-like Lectin 2; D014443:Tyrosine; C516724:PTPN11 protein, human; C509249:PTPN6 protein, human; D054592:Protein Tyrosine Phosphatase, Non-Receptor Type 11; D053824:Protein Tyrosine Phosphatase, Non-Receptor Type 6; D017027:Protein Tyrosine Phosphatases; D054593:SH2 Domain-Containing Protein Tyrosine Phosphatases