NUCLEAR IMPORT OF SERUM RESPONSE FACTOR (SRF) REQUIRES A SHORT AMINOTERMINAL NUCLEAR-LOCALIZATION SEQUENCE AND IS INDEPENDENT OF THE CASEINKINASE-II PHOSPHORYLATION SITE

Serum stimulation of resting cells is mediated at least in part at the transcriptional level by the activation of numerous genes among which c-fos constitutes a model, Serum response factor (SRF) forms a ternar y complex at the c-fos serum response element (SRE) with an accessory protein p62(TCF)/Elk-1, Both proteins are of the targets multiple phos phorylation events and their role is still unknown in the amino termin us of SRF, While the transcriptional activation domain has been mapped between amino acids 339 and 508, the DNA-binding and the dimerization domains have been mapped to between amino acids 133-235 and 168-235, respectively, no role has been proposed for the amino-terminal portion of the molecule. We demonstrate in the present work that amino acids 95 to 100 contain a stretch of basic amino acids that are sufficient t o target a reporter protein to the nucleus. Moreover, this sequence ap pears to be the only nuclear localization signal operating in SRF. Fin ally, whereas the global structure around this putative nuclear locati on signal is reminiscent of what is found in the SV40 T antigen, the c asein kinase II phosphorylation site does not determine the rate of cy to-nuclear protein transport of this protein.