The sialoadhesin CD33 is a myeloid-specific inhibitory receptor.
Activating and inhibitory receptors act in concert to regulate cellular activation. Inhibitory receptors are characterized by the presence of a characteristic sequence known as an immunoreceptor tyrosine-based inhibitory motif (ITIM) in their cytoplasmic tail. Phosphorylated ITIM serve as docking sites for the SH2-containing phosphatases which then inhibit signal transduction. CD33 is a member of the immunoglobulin superfamily and contains two immunoglobulin-like domains, a transmembrane region and a cytoplasmic tail that has two potential ITIM sequences. CD33 expression is restricted to cells of myelomonocytic lineage. The precise function of CD33 is unknown although it is a lectin that binds sialic acid residues in N- and O-glycans on cell surfaces. Co-immunoprecipitation studies demonstrate that CD33 associates with the SH2-containing tyrosine phosphatase SHP-1 in monocytes. The proximal ITIM is necessary and sufficient for SHP-1 binding which is mediated by the aminoterminal SH2 domain. Treatment of SHP-1 with a phosphopeptide representing the proximal CD33 ITIM results in increased SHP-1 enzymatic activity. CD33 exerts an inhibitory effect on tyrosine phosphorylation and Ca(2+) mobilization when co-engaged with the activating FcgammaRI receptor. This data indicates that CD33 is an inhibitory receptor that may regulate FcgammaRI signal transduction.
Ulyanova
T
T
Howard Hughes Medical Institute, Department of Pathology, Washington University School of Medicine, St. Louis, USA.
Blasioli
J
J
Woodford-Thomas
T A
TA
Thomas
M L
ML
D000818:Animals; D015703:Antigens, CD / Q000235:genetics / Q000378:metabolism*; D015214:Antigens, Differentiation, Myelomonocytic / Q000235:genetics / Q000378:metabolism*; D001665:Binding Sites; D015815:Cell Adhesion Molecules / Q000235:genetics / Q000378:metabolism*; D002478:Cells, Cultured; D004789:Enzyme Activation; D018922:HL-60 Cells; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins; D051379:Mice; D054592:Protein Tyrosine Phosphatase, Non-Receptor Type 11; D053824:Protein Tyrosine Phosphatase, Non-Receptor Type 6; D017027:Protein Tyrosine Phosphatases / Q000235:genetics / Q000378:metabolism*; D017452:Receptors, IgG / Q000378:metabolism*; D054593:SH2 Domain-Containing Protein Tyrosine Phosphatases; D063268:Sialic Acid Binding Ig-like Lectin 3; D014443:Tyrosine / Q000378:metabolism; D020298:U937 Cells; D018909:src Homology Domains
D015703:Antigens, CD; D015214:Antigens, Differentiation, Myelomonocytic; C571163:CD33 protein, human; C571165:Cd33 protein, mouse; D015815:Cell Adhesion Molecules; D047908:Intracellular Signaling Peptides and Proteins; D017452:Receptors, IgG; D063268:Sialic Acid Binding Ig-like Lectin 3; 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; C516725:Ptpn11 protein, mouse; C509248:Ptpn6 protein, mouse; D054593:SH2 Domain-Containing Protein Tyrosine Phosphatases