title: Modulation of PP2A activity by Jacalin: is it through caveolae and ER chaperones?
abstract: Plant lectins have been reported to affect the proliferation of different human cancer cell line probably by binding to the specific carbohydrate moieties. In the present study, Badan labeled single cysteine mutant (present in the caveolin-1 binding motif) of jacalin (rJacalin) was found to penetrate the target membrane, indicating a protein-protein or protein-membrane interaction apart from its primary mode of binding i.e. protein-carbohydrate interaction. Further, Jacalin treatment has resulted in the movement of the GFP-Caveolin-1 predominantly at the cell-cell contact region with much restricted dynamics. Jacalin treatment has resulted in the perinuclear accumulation of PP2A and dissociation of the PHAP1/PP2A complex. PP2A was found to act as a negative regulator of ERK signaling and a significant decrease in the phosphorylation level of MEK and AKT (T308) in A431. In addition, we have also identified several ER resident proteins including molecular chaperones like ORP150, Hsp70, Grp78, BiP of A431 cells, which were bound to the Jacalin-sepharose column. Among various ER chaperones that were identified, ORP150 was found to present on the cell surface of A431 cells.
authors.affiliation: National Centre for Cell Science, Ganeshkhind Road, University of Pune Campus, Pune, 411007, India.
authors.forename: Neesar
authors.initials: N
authors.lastname: Ahmed
authors.forename: Satyabrata
authors.initials: S
authors.lastname: Pany
authors.forename: Aejazur
authors.initials: A
authors.lastname: Rahman
authors.forename: Saumya S
authors.initials: SS
authors.lastname: Srivastava
authors.forename: Amita
authors.initials: A
authors.lastname: Sneh
authors.forename: Musti V
authors.initials: MV
authors.lastname: Krishnasastry
mesh_terms: D000595:Amino Acid Sequence; D021941:Caveolae / Q000201:enzymology*; D049109:Cell Proliferation; D004721:Endoplasmic Reticulum / Q000201:enzymology*; D000091342:Endoplasmic Reticulum Chaperone BiP; D018840:HSP70 Heat-Shock Proteins; D006801:Humans; D018832:Molecular Chaperones / Q000378:metabolism*; D037121:Plant Lectins / Q000494:pharmacology*; D011485:Protein Binding; D025941:Protein Interaction Mapping; D054648:Protein Phosphatase 2 / Q000378:metabolism*; D011506:Proteins / Q000378:metabolism; D014407:Tumor Cells, Cultured
chemical_list: D000091342:Endoplasmic Reticulum Chaperone BiP; D018840:HSP70 Heat-Shock Proteins; C000717247:HSPA5 protein, human; D018832:Molecular Chaperones; D037121:Plant Lectins; D011506:Proteins; C043696:jacalin; C050087:oxygen-regulated proteins; D054648:Protein Phosphatase 2