Homophilic Interactions Mediated by Receptor Tyrosine Phosphatases 
and 
. A CRITICAL ROLE FOR THE NOVEL EXTRACELLULAR MAM DOMAIN (*)
- Gerben C. M. Zondag(1),
- Gregory M. Koningstein(1),
- Ying-Ping Jiang(2),
- Jan Sap(2),
- Wouter H. Moolenaar(1)(§) and
- Martijn F. B. G. Gebbink(1)
- From the (1) Division of Cellular Biochemistry, The Netherlands Cancer Institute, Plesmanlaan 121, 1066 CX Amsterdam, The Netherlands and the
- (2)Department of Pharmacology, New York University Medical Center, New York, New York 10016
- § To whom correspondence should be addressed. Tel.: 31-20-512-1971; Fax: 31-20-512-1989.
Abstract
The receptor-like protein tyrosine phosphatases (RPTP) μ and RPTPκ have a modular ectodomain consisting of four fibronectin type III-like repeats, a single Ig-like domain, and a newly identified N-terminal MAM domain. The function of the latter module, which comprises about 160 amino acids and is found in diverse transmembrane proteins, is not known. We previously reported that both RPTPμ and RPTPκ can mediate homophilic cell interactions when expressed in insect cells. Here we show that despite their striking structural similarity, RPTPμ and RPTPκ fail to interact in a heterophilic manner. To examine the role of the MAM domain in homophilic binding, we expressed a mutant RPTPμ lacking the MAM domain in insect Sf9 cells. Truncated RPTPμ is properly expressed at the cell surface but fails to promote cell-cell adhesion. Homophilic cell adhesion is fully restored in a chimeric RPTPμ molecule containing the MAM domain of RPTPκ. However, this chimeric RPTPμ does not interact with either RPTPμ or RPTPκ. These results indicate that the MAM domain of RPTPμ and RPTPκ is essential for homophilic cell-cell interaction and helps determine the specificity of these interactions.
Footnotes
-
↵* This work was supported by the Dutch Cancer Society. The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore by hereby marked “advertisement” in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
-
↵1 The abbreviations used are:
- RPTP
-
receptor-like protein tyrosine phosphatase
- bp
-
base pair(s)
- kb
-
kilobase(s)
- PCR
-
polymerase chain reaction
- FCS
-
fetal calf serum
- CFDA
-
5-(and 6-)-carboxyl-2′,7′-dichlorofluorescein diacetate succinimidyl ester
- DiI
-
1,1′-dioctadecyl-3,3,3′,3′-tetramethylindocarbocyanine perchlorate
- FITC
-
fluorescein isothiocyanate
- FN III
-
fibronectin type III
- EGFR
-
epidermal growth factor receptor.
-
↵2M. Gebbink, G. Zondag, G. Koningstein, E. Feiken, R. Wubbolts, and W. Moolenaar, submitted for publication.
