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 different from CD45 is present on the membrane of human hematopoietic cells. The molecule recognized by the monoclonal antibody 143-41, which has been classified as CD148 in the VI International Workshop on Leukocyte Differentiation Antigens, was immunopurified and sequenced. The sequence obtained from N-terminus as well as from two different CNBr-digested peptides showed a close identity with a previously described tyrosine phosphatase named HPTP-eta/DEP-1. CD148 is present on all hematopoietic lineages, being expressed with higher intensity on granulocytes than on monocytes and lymphocytes. Interestingly, whereas it is clearly present on peripheral blood lymphocytes, it is poorly expressed on different lymphoid cell lines of T and B origin. When this protein tyrosine phosphatase was cocrosslinked with CD3, an inhibition of the normally observed calcium mobilization was observed. This inhibition correlates with a decrease in phospholipase C-gamma (PLC-gamma) phosphorylation 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 with the induction of tyrosine phosphorylation on several substrates, including PLC-gamma, after CD148 crosslinking, suggest the involvement of a tyrosine kinase-based signaling pathway in this process. In conclusion, the data presented show that CD148 corresponds to a previously described protein tyrosine phosphatase HPTP-eta/DEP-1 and that this molecule is involved in signal transduction in lymphocytes.
de la Fuente-García
M A
MA
Servei d'Immunologia, Servei de Medicina Interna, Hospital Clínic, Barcelona, Spain.
Nicolás
J M
JM
Freed
J H
JH
Palou
E
E
Thomas
A P
AP
Vilella
R
R
Vives
J
J
Gayá
A
A
D000595:Amino Acid Sequence; D000818:Animals; D019556:COS Cells; D019070:Cell Lineage / Q000276:immunology*; D006410:Hematopoiesis; D006412:Hematopoietic Stem Cells / Q000276:immunology*; D006801:Humans; D008969:Molecular Sequence Data; D017027:Protein Tyrosine Phosphatases / Q000096:biosynthesis* / Q000235:genetics / Q000276:immunology; D054631:Receptor-Like Protein Tyrosine Phosphatases, Class 3; D017421:Sequence Analysis; D015398:Signal Transduction / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology*
C486288:PTPRJ protein, human; D017027:Protein Tyrosine Phosphatases; D054631:Receptor-Like Protein Tyrosine Phosphatases, Class 3