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.

Identification of intracellular cavin target proteins reveals cavin-PP1alpha interactions regulate apoptosis

“…We next sought to investigate the proposed interaction between PP1α and cavin proteins in a cellular system. We focused on A431 cells that have been used extensively for caveolae studies due to an abundance of caveolae 27,28 and because, as an epidermoid skin cancer cell line, these cells have been used extensively in experiments investigating UVC irradiation, as explored later in this study 29,30 . During the course of these experiments, we determined that A431 cells (similar to several other commonly cancer cell lines such as HeLa cells) do not express Cavin2 but have significant expression of the universal components of caveolae, Cavin1, CAV1, and Cavin3.…”

Endoplasmic Reticulum Chaperones and Their Roles in the Immunogenicity of Cancer Vaccines

“…Despite its prominent role as an ER chaperone cancer vaccine ( 81 ), GRP170/ORP150 has only rarely been cited as a cancer cell-surface protein ( 15 , 82 ), but it has been identified on mouse egg oolemma ( 83 ) as well as human sperm surfaces ( 84 , 85 ). Other ER residents such as ERp5/PDI6 (PDI family) are present on tumor cell surfaces; in this case, the chaperone is involved in the release of the NK cell activating receptor MICA from tumor cell surfaces, presumably as a protective measure to avoid NK attack.…”