Abstract
The α-estrogen receptor (ERα) transcriptional activity can be regulated either by binding to the cognate ligand or by intracellular signaling pathways responsive to a variety of factors acting through cell membrane receptors. Studies carried out in HeLa and COS-1 cells demonstrated that the cross-coupling between estrogen and growth factor receptors is mediated by p21ras and requires phosphorylation of a specific serine residue (Ser 118 in the human ERα and Ser 122 in mouse ERα) located in the ERα N-terminal activation function 1 (AF-1). Likewise, in the SK-N-BE neuroblastoma cell line p21ras is involved in the cross-coupling between insulin and ERα receptors. However, in this cell line Ser 122 is not necessary for insulin-dependent activation of unliganded ERα. In addition, after insulin activation, the electrophoretic mobility associated to serine hyperphosphorylation of ERα in SK-N-BE and in COS-1 cells is different. Our study rules out the possibility of tyrosine phosporylation in unliganded ERα activation by means of transactivation studies of ERα tyrosine mutants and analysis of Tyr phosphorylation immunoreactivity. The two cofactors for steroid receptors RIP 140 and SRC-1 do not seem to be specifically involved in the insulin-induced ERα transactivation. The present study demonstrates the possibility of an alternative, cell-specific pathway of cross-coupling between intracellular and membrane receptors, which might be of importance for the understanding of the physiological significance of this mode of activation in the nervous system.
Exploiting basic principles to control the selectivity of the vapor phase catalytic oxidative cross-coupling of primary alcohols over nanoporous gold catalysts
