gms | German Medical Science

The C-terminus of the AT1-receptor has been shown to be involved in receptor signaling, independent of coupling to G-proteins. A similar pathway for the AT2 receptor has not yet been established. By performing a yeast two-hybrid screen against the C-terminus of the AT2-receptor, we isolated a protein (ATBP, AT2-receptor binding protein), which interacts directly with the AT2-receptor. The interaction was verified by immuno co-precipitation.

To further study the interaction of the two proteins in vitro investigations with PC12W cells, which endogenously express both, the AT2 receptor and ATBP but not the AT1 receptor, have been performed. Treating the cells with Angiotensin II (AngII) lead to an immediate increase of ATBP mRNA. This effect can be blocked with a selective antagonist for the AT2 receptor, confirming that the observed effect is mediated by the AT2 receptor.

Transfection of PC12W-cells with atbp lead to a 50 % decrease in cell proliferation as compared with mock transfected cells. A similar result was obtained when the AT2-receptor gene was overexpressed in PC12W-cells or the cells were stimulated with AngII. The antiproliferative action of the AT2 receptor might thus be mediated by ATBP. This is corroborated by the recent description of a new human tumor supressor gene which is identical with ATBP (Seibold et al., 2003, FASEB J., Vol. 17, p 1180-2).

The co-expression of ATBP and AT2 receptor in mouse tissues has been demonstrated by in situ hybridisation. In all tissues where the receptor is expressed, like adrenals, kidney and brain. atbp is expressed in the same expression pattern.

Taken together, our findings indicate that the antiproliferative effect of the AT2 receptor involves the activation of ATBP.