FUNCTIONAL-ANALYSIS OF A GROWTH FACTOR-RESPONSIVE TRANSCRIPTION FACTOR COMPLEX

Serum response factor (SRF) forms a ternary complex at the c-fos serum response element (SRE) with an accessory factor, Elk-1. We constructe d altered-binding specificity derivatives of SRF and Elk-1 that form a ternary complex at a mutated, inactive SRE; like Elk-1, the Elk-1 var iant only binds its target as part of a ternary complex with SRF. Simu ltaneous expression of these SRF and Elk-1 derivatives restores serum- regulated activity to the mutated SRE in transfected cells. Efficient transcriptional activation is dependent on the regulated phosphorylati on of Elk-1 C-terminal MAP kinase sites and requires the C-terminal se quences of SRF as well as SRF sequences that mediate ternary complex f ormation. These experiments provide direct evidence that SRF and Elk-1 functionally cooperate in the ternary complex at the SRE to regulate transcription.