CD148 IS A MEMBRANE-PROTEIN TYROSINE PHOSPHATASE PRESENT IN ALL HEMATOPOIETIC LINEAGES AND IS INVOLVED IN SIGNAL-TRANSDUCTION ON LYMPHOCYTES

Evidence is presented showing that a protein tyrosine phosphatase diff erent from CD45 is present on the membrane of human hematopoietic cell s. The molecule recognized by the monoclonal antibody 143-41, which ha s been classified as CD148 in the VI International Workshop on Leukocy te Differentiation Antigens, was immunopurified and sequenced. The seq uence obtained from N-terminus as well as from two different CNBr-dige sted peptides showed a close identity with a previously described tyro sine phosphatase named HPTP-eta/DEP-1. CD148 is present on all hematop oietic lineages, being expressed with higher intensity on granulocytes than on monocytes and lymphocytes, Interestingly, whereas it is clear ly present on peripheral blood lymphocytes, it is poorly expressed on different lymphoid cell lines of T and B origin. When this protein tyr osine phosphatase was cocrosslinked with CD3, an inhibition of the nor mally observed calcium mobilization was observed. This inhibition corr elates with a decrease in phospholipase C-gamma (PLC-gamma) phosphoryl ation and is similar to the one observed with CD45. In addition, it is shown that the crosslinking of the CD148 alone is also able to induce an increase in [Ca2+](i). This increase is abolished in the presence of genistein and by cocrosslinking with CD45, These data, together wit h the induction of tyrosine phosphorylation on several substrates, inc luding PLC-gamma, after CD148 crosslinking, suggest the involvement of a tyrosine kinase-based signaling pathway in this process, In conclus ion, the data presented show that CD148 corresponds to a previously de scribed protein tyrosine phosphatase HPTP-eta/DEP-1 and that this mole cule is involved in signal transduction in lymphocytes. (C) 1998 by Th e American Society of Hematology.