Endothelin induces @entity669 phosphorylation and @entity10240 association of XXXX in astrocytes.

@entity2232 @entity9703 @entity10242 @entity10240 @entity669
While the mitogen-activated protein kinase (MAPK) pathway coupled to receptor @entity669 kinases has been largely clarified, little is known about MAPK activation mediated by heterotrimeric G protein-coupled receptors. In a previous study, it has been shown that @entity2232 ( @entity2232 ) signaling through heterotrimeric G protein-coupled receptors stimulates MAPK activity in primary cultures of astrocytes (Cazaubon, S., Parker, P. J., Strosberg, A.D., and Couraud, P.O. (1993) Biochem. J. 293, 381-386). To clarify the molecular mechanism responsible for this response, involvement of the adapter proteins, @entity9703 and @entity10240 , has now been investigated. It is shown here that in these cells, @entity2232 stimulates @entity669 phosphorylation of @entity9703 , resulting in its stable association with @entity10240 but not with @entity10240 , a @entity10240 isoform with partially deleted SH2 domain. These results demonstrate that @entity669 -phosphorylated @entity9703 specifically interacts with the SH2 domain of @entity10240 . This response was rapid and transient, showing a maximum at 10 min and declining at 60 min. Interestingly, direct activation of G proteins by fluoroaluminate mimics the @entity2232 effect. In addition, a shift to a higher apparent molecular mass of @entity10242 kinase, likely reflecting its hyperphosphorylation, was also detected in @entity2232 -treated cells. These data strongly suggest that @entity2232 -induced MAPK activation is a G protein-coupled pathway that involves @entity9703 , @entity10240 , and probably @entity10242 . In conclusion, the @entity9703 - @entity10240 complex may be involved in the activation of the MAPK pathway, not only by several receptor @entity669 kinases but also by heterotrimeric G protein-coupled receptors, such as @entity2232 receptors.
