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

EMBO J. 2006 Feb 22;25(4):701-12. doi: 10.1038/sj.emboj.7600974. Epub 2006 Feb 2.


Type IIB receptor protein tyrosine phosphatases (RPTPs) are bi-functional cell surface molecules. Their ectodomains 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 RPTPmu, 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 A 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Catalytic Domain / physiology
  • Cell Adhesion / physiology
  • Cell Line
  • Crystallography, X-Ray
  • Fibronectins / chemistry
  • Humans
  • Mutagenesis, Site-Directed
  • Protein Structure, Tertiary / physiology
  • Protein Tyrosine Phosphatases / chemistry*
  • Protein Tyrosine Phosphatases / genetics
  • Protein Tyrosine Phosphatases / metabolism
  • Receptor-Like Protein Tyrosine Phosphatases, Class 2
  • Structural Homology, Protein


  • Fibronectins
  • fibronectin type III like peptide, human
  • PTPRM protein, human
  • Protein Tyrosine Phosphatases
  • Receptor-Like Protein Tyrosine Phosphatases, Class 2