PHOSPHACAN, A CHONDROITIN SULFATE PROTEOGLYCAN OF BRAIN THAT INTERACTS WITH NEURONS AND NEURAL CELL-ADHESION MOLECULES, IS AN EXTRACELLULARVARIANT OF A RECEPTOR-TYPE PROTEIN-TYROSINE-PHOSPHATASE

We have identified cDNA clones encoding a chondroitin sulfate proteogl ycan of rat brain (previously designated 3F8 and now named phosphacan) that binds to neurons and neural cell-adhesion molecules. A sequence of 1616 amino acids deduced from a 4.8-kb open reading frame contains the N-terminal amino acid sequence of the 3F8 core glycoprotein as wel l as four internal CNBr, tryptic, and endoproteinase Lys-C peptide seq uences from the proteoglycan. The deduced amino acid sequence, beginni ng with a 24-amino acid signal peptide, reveals an N-terminal domain o f 255 amino acids homologous to carbonic anhydrases. The entire amino acid sequence deduced from our cDNA clones corresponds to the extracel lular portion of a human receptor-type protein tyrosine phosphatase (R PTPzeta/beta) with which it has 76% identity, and the proteoglycan may represent an mRNA splicing variant of the larger transmembrane protei n. RNA analysis demonstrated that a probe to the N-terminal carbonic a nhydrase domain of the proteoglycan hybridizes with rat brain mRNA of 9.5, 8.4, and 6.4 kb, whereas probes to the phosphatase domains hybrid ize with only the 9.5 -kb message and with the 6.4-kb message (which c orresponds to a previously identified variant of the transmembrane pro tein in which half of the extracellular domain is deleted). The 30 N-t erminal amino acids of the 3H1 chondroitin/keratan sulfate proteoglyca n of brain are identical to those of the 3F8 proteoglycan, and six int ernal tryptic peptide sequences also matched those found in sequenced peptides of the 3F8 proteoglycan and/or amino acid sequences deduced f rom the cDNA clones. We therefore conclude that the 3H1 chondroitin/ke ratan sulfate proteoglycan and the 3F8 choridroitin sulfate proteoglyc an represent glycosylation and possible extracellular splicing variant s of a receptor-type protein tyrosine phosphatase. These proteoglycans may modulate cell interactions and other developmental processes in n ervous tissue through heterophilic binding to cell-surface and extrace llular matrix molecules, and by competition with ligands of the transm embrane phosphatase.