CD22 attenuates calcium signaling by potentiating plasma membrane calcium-ATPase activity.
Binding of antigen to the B cell receptor induces a calcium response, which is required for proliferation and antibody production. CD22, a B cell surface protein, inhibits this signal through mechanisms that have been obscure. We report here that CD22 augments calcium efflux after B cell receptor crosslinking. Inhibition of plasma membrane calcium-ATPase (PMCA) attenuated these effects, as did disruption by homologous recombination of the gene encoding PMCA4a and PMCA4b. PMCA coimmunoprecipitated with CD22 in an activation-dependent way. CD22 cytoplasmic tyrosine residues were required for association with PMCA and enhancement of calcium efflux. Moreover, CD22 regulation of efflux and the calcium response required the tyrosine phosphatase SHP-1. Thus, SHP-1 and PMCA provide a mechanism by which CD22, a tissue-specific negative regulator, can affect calcium responses.
Chen
Jie
J
Department of Pathology, Tufts University School of Medicine, Boston, Massachusetts 02111, USA.
McLean
Paul A
PA
Neel
Benjamin G
BG
Okunade
Gbolahan
G
Shull
Gary E
GE
Wortis
Henry H
HH
D000818:Animals; D015703:Antigens, CD / Q000378:metabolism*; D000944:Antigens, Differentiation, B-Lymphocyte / Q000378:metabolism*; D001402:B-Lymphocytes / Q000201:enzymology / Q000378:metabolism; D002118:Calcium / Q000378:metabolism; D020013:Calcium Signaling / Q000502:physiology*; D000252:Calcium-Transporting ATPases / Q000378:metabolism*; D015815:Cell Adhesion Molecules; D002462:Cell Membrane / Q000201:enzymology / Q000378:metabolism*; D002645:Chickens / Q000378:metabolism; D047908:Intracellular Signaling Peptides and Proteins; D037102:Lectins / Q000378:metabolism*; D051379:Mice; D010766:Phosphorylation; D053824:Protein Tyrosine Phosphatase, Non-Receptor Type 6; D017027:Protein Tyrosine Phosphatases / Q000378:metabolism; D011947:Receptors, Antigen, B-Cell / Q000378:metabolism; D051918:Sialic Acid Binding Ig-like Lectin 2; D013997:Time Factors
D015703:Antigens, CD; D000944:Antigens, Differentiation, B-Lymphocyte; C497868:Cd22 protein, mouse; D015815:Cell Adhesion Molecules; D047908:Intracellular Signaling Peptides and Proteins; D037102:Lectins; D011947:Receptors, Antigen, B-Cell; D051918:Sialic Acid Binding Ig-like Lectin 2; D053824:Protein Tyrosine Phosphatase, Non-Receptor Type 6; D017027:Protein Tyrosine Phosphatases; C509248:Ptpn6 protein, mouse; D000252:Calcium-Transporting ATPases; D002118:Calcium