Cell-cell adhesion mediated by a receptor-like protein tyrosine phosphatase.
Receptor-like protein tyrosine phosphatases (receptor-PTPs) represent a novel family of transmembrane proteins that are thought to play important roles in cellular regulation. They consist of a cytoplasmic catalytic region, a single transmembrane segment and an extracellular, putative ligand-binding domain, but the nature of their physiological ligands is unknown. We have recently cloned a new receptor-PTP (RPTP mu), the ectodomain of which includes an Ig-like and four fibronectin type III-like domains, suggesting that RPTP mu may be involved in cell-cell or cell-matrix interactions. To test this hypothesis, we expressed RPTP mu in insect Sf9 cells using recombinant baculovirus. We demonstrate that RPTP mu dramatically promotes cell-to-cell adhesion in a homophilic, Ca(2+)-independent manner. No adhesion is observed in Sf9 cells expressing a chimeric RPTP mu molecule containing the extracellular domain of the epidermal growth factor receptor. Furthermore, cells expressing an enzymatically inactive, point-mutated RPTP mu or a truncated form of RPTP mu, lacking the entire catalytic region, show adhesive properties indistinguishable from those of wild-type RPTP mu, indicating that the catalytic domain is not essential for RPTP mu-mediated adhesion. These results assign a physiological role for RPTP mu in signaling cell-cell recognition.
Division of Cellular Biochemistry, The Netherlands Cancer Institute, Amsterdam.
M F
MF
Gebbink
G C
GC
Zondag
R W
RW
Wubbolts
R L
RL
Beijersbergen
I
I
van Etten
W H
WH
Moolenaar
D000818:Animals; D001483:Base Sequence; D002118:Calcium / Q000378:metabolism; D002384:Catalysis; D002448:Cell Adhesion; D002460:Cell Line; D004247:DNA; D006801:Humans; D006863:Hydrogen-Ion Concentration; D008565:Membrane Proteins / Q000378:metabolism*; D008969:Molecular Sequence Data; D009036:Moths; D017027:Protein Tyrosine Phosphatases / Q000378:metabolism*; D054623:Receptor-Like Protein Tyrosine Phosphatases, Class 2; D054635:Receptor-Like Protein Tyrosine Phosphatases, Class 8; D011956:Receptors, Cell Surface / Q000378:metabolism*
D008565:Membrane Proteins; D011956:Receptors, Cell Surface; D004247:DNA; C516862:PTPRN protein, human; D017027:Protein Tyrosine Phosphatases; D054623:Receptor-Like Protein Tyrosine Phosphatases, Class 2; D054635:Receptor-Like Protein Tyrosine Phosphatases, Class 8; D002118:Calcium