ASSOCIATION OF THE TRANSMEMBRANE-4 SUPERFAMILY MOLECULE CD53 WITH A TYROSINE PHOSPHATASE-ACTIVITY

Cell surface proteins of the transmembrane 4 superfamily (TM4SF) are a newly characterized family of proteins which are presumed to span the plasma membrane four times. The function of this family of molecules is poorly understood, but based on monoclonal antibody studies there i s some evidence that they may be involved in transmembrane signal tran sduction and regulation of cell proliferation, differentiation, or bot h, in a number of different cell types. CD53 is a member of this famil y that is expressed on leukocytes, and transduces activation signals t hrough unknown mechanisms that may involve phosphorylation events. How ever, CD53 has never been shown to associate directly with kinases. He re, we show by immunoprecipitation from cell lysates of lymph nodes an d a thymoma cell line, that immune complexes of rat CD53 contain tyros ine phosphatase activity. The CD53-associated phosphatase was able to dephosphorylate in vitro the phosphorylated tyrosine kinase Lck, as we ll as a synthetic substrate, and its activity was abrogated by a tyros ine phosphatase inhibitor. Although its identity has not been establis hed, it is clear from depletion experiments that it is not CD45. CD63, a second member of the TM4SF, also co-precipitates a phosphatase acti vity from rat basophilic leukemia cells. These results demonstrate tha t the TM4SF members associate with tyrosine phosphatases. It seems pos sible that such associated phosphatases may contribute to the signal t ransduction capacity of TM4SF molecules.