Type-2A protein phosphatase ( @entity4333 ) is a key regulator in many different cell signaling pathways and an important determinant in tumorigenesis. One of the signaling targets of @entity4333 is the mitogen-activated protein kinase (MAPK/ERK) cascade. In this study, we wanted to determine whether @entity4333 could be involved in regulation of @entity204 receptor activity through its capacity to regulate MAPK/ERK. To this end, we studied the effects of two different routes of protein phosphatase inhibition on @entity204 receptor-mediated apoptosis. We demonstrated that the apoptosis mediated by Fas, @entity310 , and @entity2205 in U937 cells is suppressed by calyculin A, an inhibitor of type-1 and type-2A protein phosphatases. The inhibition of the protein phosphatase activity was shown to subsequently increase the MAPK activity in these cells, and the level of activation corresponded to the degree of suppression of cytokine-mediated apoptosis. A more physiological inhibitor, the intracellular @entity4333 inhibitor protein I2( @entity4333 ), protected transfected HeLa cells in a similar way from Fas-mediated apoptosis and induced activation of MAPK in I2( @entity4333 ) transfected cells. A corresponding inhibition could also be obtained by stable transfection with a constitutively active form of the MAPK kinase, @entity12363 (also referred to as @entity12363 ). The inhibitor-mediated protection was highly efficient in preventing early stages of apoptosis, as no @entity8186 cleavage occurred in these cells. The observed apoptosis suppression is likely to facilitate the @entity5 -promoting effect of a range of different type-2A protein phosphatase inhibitors, and could explain the reported @entity5 association of I2( @entity4333 ).

Type-2A protein phosphatase activity is required to maintain XXXX receptor responsiveness.

@entity310 :: ('7124', 'Gene') :: ['TNF-alpha'] @entity2205 :: ('8743', 'Gene') :: ['TRAIL'] @entity5 :: ('MESH:D009369', 'Disease') :: ['tumor'] @entity8186 :: ('841', 'Gene') :: ['caspase-8'] @entity204 :: ('MESH:D003643', 'Disease') :: ['death'] @entity4333 :: ('5524', 'Gene') :: ['PP2A'] @entity12363 :: ('5604', 'Gene') :: ['MEK1', 'MKK1']
@entity204 :: (MESH:D003643,Disease) :: ['death']
