Receptor-like protein tyrosine phosphatase gamma (RPTPgamma), but not PTPzeta/RPTPbeta, inhibits nerve-growth-factor-induced neurite outgrowth in PC12D cells.

Receptor-like protein tyrosine phosphatase gamma (RPTPgamma) and PTPzeta/RPTPbeta are RPTPs which structurally resemble each other and form a distinct RPTP family. Both molecules are highly expressed in the central nervous system (CNS), though RPTPgamma is distributed also in several peripheral tissues. To date, the functional differences between RPTPgamma and PTPzeta in neuronal cells have not been made clear because their substrate and ligand molecules have not been fully elucidated. To address this issue, we established PC12D cell transfectants stably expressing rat RPTPgamma or PTPzeta and analyzed the effects on cellular response to nerve growth factor (NGF). Compared with the parent PC12D cells which extend neurites vigorously in response to NGF, the transfectants expressing RPTPgamma showed almost no neurite outgrowth. In contrast, neurite extension in PTPzeta-expressing clones on NGF treatment was the same as in parent cells. We investigated differences in tyrosine phosphorylation levels in the cellular proteins in these cells after the NGF treatment before morphological charges appeared. Despite the lack of a response, major proteins and MAP kinase in RPTPgamma-expressing PC12D cells displayed normal tyrosine phosphorylation changes on NGF treatment. However, tyrosine phosphorylation levels in the protein components purified with p13(suc1) agarose (p13(suc1) complex) from RPTPgamma-expressing cells were different from those of the control cells. (1) Tyrosine-phosphorylation levels of 140- and 117-kD proteins were significantly reduced. (2) Rapid tyrosine phosphorylation of 58-kD protein induced by NGF was absent. (3) Activities of tyrosine kinases and protein kinase C in the p13(suc1) complex were markedly reduced. We found that the p13(suc1) complex also contained cytoskeletal proteins such as MAP2 and neurofilaments, but their phosphorylation levels were not different. These results indicate that RPTPgamma and PTPzeta have different substrate specificities, and RPTPgamma inhibits NGF-induced neurite outgrowth of PC12D cells through modulation of the p13(suc1) complex. Copyright 2001 S. Karger AG, Basel