TULA-family proteins: an odd couple

Two members of the TULA family (TULA/STS-2/UBASH3A and TULA-2/STS-1/UBASH3B) recently emerged as novel regulators of several cellular functions. The degree of structural similarity between the TULA-family proteins is typical for proteins that belong to the same family. Furthermore, the experiments with knockout mice lacking these proteins may be interpreted as suggesting that functions of TULA-family proteins in T lymphocytes overlap. At the same time, TULA and TULA-2 exhibit clear functional dissimilarities, starting with the finding that a conserved phosphatase domain present in both proteins exhibits remarkable differences in enzymatic activity; TULA-2 is an active phosphatase capable of dephosphorylating multiple tyrosine-phosphorylated proteins, whereas the phosphatase activity of TULA is extremely low. In contrast, TULA, but not TULA-2, facilitates growth factor withdrawal-induced apoptosis in T cells. In spite of their apparent importance, the functional role of TULA-family proteins is not well understood. In particular, the role of functional dissimilarities between them remains unclear.