Introduction: CD148 is a new Cluster of Differentiation defined in the VI International Workshop on Leucocyte Differentation Antigens (WLDA). Although this molecule was officially recognized at VI WLDA it represents the hematopoietic form of a previously described membrane protein tyrosine phosphatase HPTPη/DEP-1. In the present work we were interested to know whether CD148 could influence the signal transduction through the antigen receptor in a similar way to CD45, the main protein tyrosine phosphatase expressed on the membrane of lymphocytes.Materials and Methods: Cells previously coated with CD3, CD148 or both were stimulated with rabbit anti-mouse antisera. Ca 2 + mobilization after cell stimulation was analyzed by computer-aided fluorescence imaging using lymphocytes loaded with fura2/AM. Tyrosine-phosphorylated protein patterns were detected by immunoblotting.Results: When CD148 was co-cross-linked with CD3 a clear inhibition of the subsequent calcium mobilization was observed. Furthermore, the pattern of protein tyrosine phosphorylation after CD3 cross-linking was also modified when it was co-cross-linked with CD148. In addition, we observed that the stimulation of lymphocytes with CD148 alone was able to induce an increase in [Ca 2 + ] i which was abolished in the presence of genistein and by co-cross-linking with CD45. These data, together with the induction of tyrosine phosphorylation after CD148 cross-linking, suggest the involvement of tyrosine kinases based signalling pathways in this process.Conclusion: Our data show that CD148, a recently described membrane protein tyrosine phosphatase, induces tyrosine phosphorylation probably by the activation of protein tyrosine kinase(s) and could be involved in CD3 signalling in T lymphocytes.