Cell surface glycoprotein PZR is a major mediator of concanavalin A-induced cell signaling.
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 in Escherichia 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.
Zhao
Runxiang
R
Division of Hematology/Oncology, Department of Medicine, Vanderbilt-Ingram Cancer Center, Vanderbilt University, Nashville, Tennessee 37232-6307, USA.
Guerrah
Abdelmadjid
A
Tang
Hua
H
Zhao
Z Joe
ZJ
D016475:3T3 Cells; D020816:Amino Acid Motifs; D000818:Animals; D015153:Blotting, Western; D002460:Cell Line; D003208:Concanavalin A / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D004926:Escherichia coli / Q000378:metabolism; D006367:HeLa Cells; D006801:Humans; D015151:Immunoblotting; D051379:Mice; D015688:Oncogene Protein pp60(v-src) / Q000378:metabolism; D010766:Phosphorylation; D011233:Precipitin Tests; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D015398:Signal Transduction; D013997:Time Factors; D014443:Tyrosine / Q000378:metabolism
D003208:Concanavalin A; D014443:Tyrosine; D015688:Oncogene Protein pp60(v-src)