Details

Autor(en) / Beteiligte

• Valeriu B. Cismasiu
• Stefan A. Denes
• Helmut Reiländer
• Hartmut Michel
• Stefan E. Szedlacsek

Titel

The MAM (Meprin/A5-protein/PTPmu) Domain Is a Homophilic Binding Site Promoting the Lateral Dimerization of Receptor-like Protein-tyrosine Phosphatase Î

Ist Teil von

• The Journal of biological chemistry, 2004-06, Vol.279 (26), p.26922

Ort / Verlag

American Society for Biochemistry and Molecular Biology

Erscheinungsjahr

2004

Link zum Volltext

Quelle

Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals

Beschreibungen/Notizen

• The MAM ( m eprin/ A 5-protein/PTP m u) domain is present in numerous proteins with diverse functions. PTPμ belongs to the MAM-containing subclass of protein-tyrosine phosphatases (PTP) able to promote cell-to-cell adhesion. Here we provide experimental evidence that the MAM domain is a homophilic binding site of PTPμ. We demonstrate that the MAM domain forms oligomers in solution and binds to the PTPμ ectodomain at the cell surface. The presence of two disulfide bridges in the MAM molecule was evidenced and their integrity was found to be essential for MAM homophilic interaction. Our data also indicate that PTPμ ectodomain forms oligomers and mediates the cellular adhesion, even in the absence of MAM domain homophilic binding. Reciprocally, MAM is able to interact homophilically in the absence of ectodomain trans binding. The MAM domain therefore contains independent cis and trans interaction sites and we predict that its main role is to promote lateral dimerization of PTPμ at the cell surface. This finding contributes to the understanding of the signal transduction mechanism in MAM-containing PTPs.