Angiotensin II type 2 receptor mediates programmed cell death

The function of the recently discovered angiotensin II type 2 (AT(2)) receptor remains elusive. This receptor is expressed abundantly in fetus, but scantily in adult tissues except brain, adrenal medulla, and atretic ovary. In this study, rye demonstrated that this receptor mediates programmed cell death (apoptosis). We observed this effect in PC12W cells (rat pheochromocytoma cell line) and R3T3 cells (mouse fibroblast cell line), which express abundant AT(2) receptor but not AT(1) receptor, The cellular mechanism appears to involve the dephosphorylation of mitogen-activated protein kinase (MAP kinase). Vanadate, a protein-tyrosine-phosphatase inhibitor, attenuated the dephosphorylation of MAP kinases by the AT(2) receptor and restored the apoptotic changes, Antisense oligonucleotide to MAP kinase phosphatase 1 inhibited the AT(2) receptor-mediated MAP kinase dephosphorylation and blocked the AT(2) receptor-mediated apoptosis, These results suggest that protein-tyrosine-phosphatase, including MAP kinase phosphatase I activated by the AT(2) receptor, is involved in apoptosis, We hypothesize that this apoptotic function of the AT(2) receptor may play an important role in developmental biology and pathophysiology.