CD22 Stimulates Plasma Membrane Calcium Pumps

Science's STKE  01 Jun 2004:
Vol. 2004, Issue 235, pp. tw194-TW194
DOI: 10.1126/stke.2352004TW194

CD22 is a plasma membrane protein that inhibits B cell signaling. Chen et al. report that CD22 inhibited calcium signaling through a mechanism that could be inhibited by blocking the activity of the plasma membrane calcium pump (PMCA) in two B cell lines that had been engineered to express CD22. Activation of the cells with antibodies to immunoglobulin M (IgM) produced an increase in calcium efflux in CD22-expressing cells compared with that in CD22-deficient cells. The presence of PMCAs in B cells was confirmed by immunoblotting, and the abundance of PMCA was unchanged by the presence or absence of CD22. In activated B cells, PMCA and CD22 coimmunoprecipitated. This interaction, and negative regulation of B cell signaling, was blocked in cells expressing a mutant of CD22 lacking the phosphorylatable tyrosine residues or in cells deficient in PMCA4. The negative regulation of B cell signaling by CD22 also required the phosphatase SHIP-1, because cells deficient in SHIP-1 did not exhibit increased calcium efflux or decreased calcium signaling by CD22. Thus, CD22 appears to recruit SHIP-1 and interact with PMCA to limit calcium signaling by enhancing calcium efflux through the plasma membrane.

J. Chen, P. A. McClean, B. G. Neel, G. Okunade, G. E. Shull, H. H. Wortis, CD22 attenuates calcium signaling by potentiating plasma membrane calcium-ATPase activity. Nat. Immunol. 5, 651-657 (2004). [Online Journal]