Cell Surface Glycoprotein PZR Is a Major Mediator of Concanavalin A-induced Cell Signaling

• Published in: The Journal of biological chemistry Vol. 277; no. 10; pp. 7882 - 7888
• Main Authors: Zhao, Runxiang, Guerrah, Abdelmadjid, Tang, Hua, Zhao, Z. Joe
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 08.03.2002; American Society for Biochemistry and Molecular Biology
• Subjects: 3T3 Cells; Amino Acid Motifs; Animals; Blotting, Western; Cell Line; Concanavalin A - metabolism; Dose-Response Relationship, Drug; Escherichia coli - metabolism; HeLa Cells; Humans; Immunoblotting; Mice; Oncogene Protein pp60(v-src) - metabolism; Phosphorylation; Precipitin Tests; Protein Binding; Protein Structure, Tertiary; Signal Transduction; Time Factors; Tyrosine - metabolism
• ISSN: 0021-9258; 1083-351X
• DOI: 10.1074/jbc.M111914200

PZR is an immunoglobulin superfamily cell surface protein containing a pair of immunoreceptor tyrosine-based inhibitory motifs. As a glycoprotein, PZR displays a strong association with concanavalin A (ConA), a member of the plant lectin family. Treatment of several cell lines with ConA caused tyrosine phosphorylation of a major cellular protein. Immunoblotting and immunoprecipitation studies indicated that this protein corresponded to PZR. Tyrosine phosphorylation of PZR was accompanied by recruitment of SHP-2 and was inhibited by PP1, a selective inhibitor of the Src family tyrosine kinases. Furthermore, c-Src was constitutively associated with PZR and was activated upon treatment of cells with ConA. Moreover, tyrosine phosphorylation of PZR was markedly enhanced in v-Src-transformed NIH-3T3 cells and was predominant inEscherichia coli cells co-expressing c-Src. Expression of an intracellular domain-truncated form of PZR in HT-1080 cells affected cell morphology and had a dominant negative effect on ConA-induced tyrosine phosphorylation of PZR, activation of c-Src, and agglutination of the cells. Together, the data indicate that PZR is a major receptor of ConA and has an important role in cell signaling via c-Src. Considering the various biological activities of ConA, the study of PZR may have major therapeutic implications.