TYROSINE PHOSPHORYLATION OF THE C-CBL PROTOONCOGENE PRODUCT MEDIATED BY CELL-SURFACE ANTIGEN CD38 IN HL-60 CELLS

The human cell surface antigen CD38 is a 46-kDa type II transmembrane glycoprotein with a short N-terminal cytoplasmic domain and a long Cys rich C-terminal extracellular one. We demonstrated previously that th e extracellular domain of CD38 has NAD(+) glycohydrolase (NADase) acti vity and that the ecto-form NADase activity induced in HL-60 cells dur ing cell differentiation by retinoic acid is due to CD38. In the prese nt study, we investigated the intracellular signaling mediated by CD38 in retinoic acid differentiated HL-60 cells with an anti-CD38 monoclo nal antibody, The addition of anti-CD38 monoclonal antibody to the cel ls induced rapid tyrosine phosphorylation of the cellular proteins wit h molecular weights of 120,000, 87,000, and 77,000, An increase in tyr osine kinase activity in the anti-phosphotyrosine immunoprecipitates o f the cells was also observed after the addition of anti-CD38 monoclon al antibody, Moreover, one of the prominent tyrosine-phosphorylated pr oteins stimulated by the anti-CD38 monoclonal antibody was identified as the c-cbl protooncogene product, p120(c-cbl). These results indicat ed that tyrosine phosphorylation of cellular proteins, including p120( c-cbl), is possibly involved in transmembrane signaling mediated by CD 38.