Molecular analysis of receptor protein tyrosine phosphatase μ-mediated cell adhesion

Type IIB receptor protein tyrosine phosphatases ( RPTPs) are bi- functional cell surface molecules. Their ecto-domains mediate stable, homophilic, cell- adhesive interactions, whereas the intracellular catalytic regions can modulate the phosphorylation state of cadherin/ catenin complexes. We describe a systematic investigation of the cell- adhesive properties of the extracellular region of RPTP mu, a prototypical type IIB RPTP. The crystal structure of a construct comprising its N- terminal MAM ( meprin/ A5/ mu) and Ig domains was determined at 2.7 angstrom resolution; this assigns the MAM fold to the jelly- roll family and reveals extensive interactions between the two domains, which form a rigid structural unit. Structure- based site-directed mutagenesis, serial domain deletions and cell-adhesion assays allowed us to identify the four N- terminal domains ( MAM, Ig, fibronectin type III ( FNIII)- 1 and FNIII- 2) as a minimal functional unit. Biophysical characterization revealed at least two independent types of homophilic interaction which, taken together, suggest that there is the potential for formation of a complex and possibly ordered array of receptor molecules at cell contact sites.