Activation of the mitogen-activated protein kinase pathway through p75NTR: a common mechanism for the XXXX family.

@entity3647 @entity13714 @entity2252 @entity2250 @entity669 @entity1366
Neurotrophins interact with two distinct classes of cell-surface receptors, the @entity2250 receptor @entity669 kinase family and the common @entity2252 receptor @entity3647 ( @entity13714 ). For many years, the biological role of @entity3647 ( @entity13714 ) remained obscure, being relegated to modulating @entity2250 binding of neurotrophins. Recently, the importance of @entity3647 ( @entity13714 ) as a signaling receptor in itself has become increasingly clear. The signals initiated by @entity3647 ( @entity13714 ) are likely to be as complex as those for the @entity2250 family and probably depend on the cell system in which such signaling is being studied. In this study, all members of the @entity2252 family were demonstrated to be capable of stimulating @entity3647 ( @entity13714 )-mediated activation of the mitogen-activated protein kinase (MAPK) family ( @entity1366 ). This activation is rapid and transient, peaking at 5-15 min, depending on the cell system. The classical MAPK cascade consists of the reaction series Ras-Raf-MEK-MAPK. The @entity3647 ( @entity13714 )-induced MAPK activation is MEK dependent but Raf independent. This result implies that @entity2252 activation of @entity3647 ( @entity13714 ) results in some cascade (as yet unknown) that bypasses Raf and converges on MEK to result in activation of MAPK. This activated MAPK is then able to translocate to the nucleus. The effect of this MAPK activation on cell survival is dependent on cell type. These results support the concept that signaling from the @entity3647 is more diverse and extensive than previously believed.
