PHOSPHORYLATION-DEPENDENT FORMATION OF A QUATERNARY COMPLEX AT THE C-FOS SRE

The rapid and transient induction of the human proto-oncogene c-fos in response to a variety of stimuli depends on the serum response elemen t (SRE). In vivo footprinting experiments show that this promoter elem ent is bound by a multicomponent complex including the serum response factor (SRF) and a ternary complex factor such as Elk-1. SRF is though t to recruit a ternary complex factor monomer into an asymmetric compl ex. In this report, we describe a quaternary complex over the SRE whic h, in addition to an SRF dimer, contains two Elk-1 molecules. Its form ation at the SRE is strictly dependent on phosphorylation of S-383 in the Elk-1 regulatory domain and appears to involve a weak intermolecul ar association between the two Elk-1 molecules. The influence of mutat ions in Elk-1 on quaternary complex formation in vitro correlates with their effect on the induction of c-fos reporter expression in respons e to mitogenic stimuli in vivo.