Function of the Pointed (PNT) domain in C. elegans

The PNT domain is conserved in only one-third of the ETS proteins and appears to provide distinct functions to different family members. We have previously determined the structure of the Ets-1 PNT domain (Slupsky et al. 1998) and it has been recently reported that a more commonly found structural domain, termed the SAM domain, is highly similar in structure to the PNT domain. The role of this domain in proteins involved in gene expression and signal transduction is of growing interest. We discovered that the PNT domains of Ets-1 and Ets-2 serve as docking sites for the MAPK ERK2 that phosphorylates a nearby site and enhances the activation activity of Ets-1. In addition, the PNT domain helps in the recruitment of the co-activators CBP/p300. We are also investigating the function of the PNT domain of the C. elegans ETS protein EDT-1. We have determined that edt-1 is expressed specifically in seam cells of the worm. These cells serve as stem cells for the larval epidermis and undergo cycles of cell division, migration, adhesion and fusion during each larval stage. Mutant worms with disruptions in the edt-1 gene are consistent with these roles. We plan to use these phenotypes to perform forward genetic screens provide insight into EDT-1 biology and the function of the PNT domain.