HEMOPHILIC INTERACTIONS MEDIATED BY RECEPTOR TYROSINE PHOSPHATASE-MU AND PHOSPHATASE-KAPPA - A CRITICAL ROLE FOR THE NOVEL EXTRACELLULAR MAM DOMAIN

The receptor-like protein tyrosine phosphatases (RPTP) mu and RPTP kap pa have a modular ectodomain consisting of four fibronectin type III-l ike repeats, a single Ig-like domain, and a newly identified N-termina l MAM domain, The function of the latter module, which comprises about 160 amino acids and is found in diverse transmembrane proteins, is no t known, We previously reported that both RPTP mu, and RPTP kappa can mediate homophilic cell interactions when expressed in insect cells, H ere we show that despite their striking structural similarity, RPTP mu and RPTP kappa fail to interact in a heterophilic manner, To examine the role of the MAM domain in hemophilic binding, we expressed a mutan t RPTP mu lacking the MAM domain in insect Sf9 cells, Truncated RPTP m u is properly expressed at the cell surface but fails to promote cell- cell adhesion, Homophilic cell adhesion is fully restored in a chimeri c RPTP mu molecule containing the MAM domain of RPTP kappa. However, t his chimeric RPTP mu does not interact with either RPTP mu or RPTP kap pa, These results indicate that the MAM domain of RPTP mu and RPTP kap pa is essential for homophilic cell cell interaction and helps determi ne the specificity of these interactions.