Rapid Extranuclear Signaling by the Estrogen Receptor (ER): MNAR Couples ER and Src to the MAP Kinase Signaling Pathway

Activation of Src by the ER and the MNAR adaptor protein. ER, in the presence of estrogen (E2), interacts with MNAR and Src to form a stable ternary complex through a specific estrogen-induced interaction between the AF-2 domain in ER and LXXLL motifs in MNAR. Additional stabilizing interactions are provided by the ER interaction with the SH2 domain of Src. PXXP motifs in MNAR interact with the SH3 domain of Src and convert Src from an inactive “closed” conformation to an active “open conformation.” See text for details.