The vast diversity of cellular types and behaviours is mainly the result of combinatorial interactions between a limited number of transcription factors and cellular signalling pathways whose activity is stringently controlled by developmental, cellular and extracellular cues. Studies of serum response factor (SRF) have provided a paradigm for such interactions for some years. Recent advances have shown that two families of SRF cofactors, the ternary complex factors (TCFs) and the myocardin-related transcription factors (MTRFs), are regulated by separate signalling pathways and thereby control SRF target genes differentially. The actin cytoskeleton is both an upstream regulator of MRTF activity, with monomeric actin directly acting as a signal transducer, and a downstream effector, because of the many cytoskeletal target genes. Here we discuss how the competition among cofactors might integrate these distinct signalling pathways into a specific transcriptional response and biological function.