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Fig. 7. Model of the assembly and function of the ER macromolecular complex. In the absence of hormone, ER {alpha} does not interact with p85 or p130Cas (1). Estradiol triggers association of ER {alpha}, c-Src, the p85 subunit of PI 3-kinase (PI3K) and p130Cas in a macromolecular complex (2) and activates the c-Src kinase leading to p130Cas-dependent Erk1/2 phosphorylation (see Fig. 5). Increased amount of cellular p130Cas (3) induces a further activation of the c-Src kinase and of the downstream Erk1/2 MAPK pathways.