Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P20020 (adenosine triphosphatase)
 3,299 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

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.
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PMID:CD22 attenuates calcium signaling by potentiating plasma membrane calcium-ATPase activity. 1513 9

Tumor cells often exist in a hypoxic microenvironment, which produces acidic metabolites. To survive in this harsh environment, tumor cells must exhibit a dynamic cytosolic pH regulatory system. Vacuolar H(+)-adenosine triphosphatase (V-ATPase) is considered to play an important role in the regulation of the acidic microenvironment of some tumors. In this study, we made an investigation on the expression and functional role of V-ATPase in native human hepatocellular carcinoma (HCC). The results showed that the messenger RNA and protein expression levels of V-ATPase subunit ATP6L in native human HCC tissues were markedly increased, compared with normal liver tissues. Immunohistochemical analysis further confirmed the enhanced expression of V-ATPase ATP6L in human HCC cells and revealed that V-ATPase ATP6L was distributed in the cytoplasm and plasma membrane of HCC cells. The results from immunofluorescence and biotinylation of cell surface protein showed that V-ATPase ATP6L was conspicuously located in the plasma membrane of human HCC cells. Bafilomycin A1, a specific V-ATPase inhibitor, markedly slowed the intracellular pH (pHi) recovery after acid load in human HCC cells and retarded the growth of human HCC in orthotopic xenograft model. These results demonstrated that V-ATPase is up-regulated in human HCC and involved in the regulation of pHi of human HCC cells. The inhibition of V-ATPase can effectively retard the growth of HCC, indicating that V-ATPase may play an important role in the development and progression of human HCC, and targeting V-ATPase may be a promising therapeutic strategy against human HCC.
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PMID:Expression and functional role of vacuolar H(+)-ATPase in human hepatocellular carcinoma. 2296 3