MITOGENIC STIMULATION OF RESTING T-CELLS CAUSES RAPID PHOSPHORYLATIONTRANSCRIPTION FACTOR LSF AND INCREASED DNA-BINDING ACTIVITY

The mammalian transcription factor LSF (CP2/LBP-1c) binds cellular pro moters modulated by cell growth signals. We demonstrate here that LSF- DNA-binding activity is strikingly regulated by induction of cell grow th in human peripheral T lymphocytes. Within 15 min of mitogenic stimu lation of these cells, the level of LSF-DNA-binding activity increased by a factor of five. The level of LSF protein in the nucleus remained constant throughout this interval. However, a rapid decrease in the e lectrophoretic mobility of LSF, attributable to phosphorylation, corre lated with the increase in DNA-binding activity. pp44 (ERK1) phosphory lated LSF in vitro on the same residue that was phosphorylated in vivo , specifically at amino acid position 291, as indicated by mutant anal ysis. As direct verification of the causal relationship between phosph orylation and DNA-binding activity, treatment in vitro of LSF with pho sphatase both increased the electrophoretic mobility of the protein an d decreased LSF-DNA-binding activity. This modulation of LSF-DNA-bindi ng activity as T cells progress from a resting to a replicating state reveals that LSF activity is regulated during cell growth and suggests that LSF regulates growth-responsive promoters.