Multidomain STS/TULA proteins are novel cellular regulators.

Proteins of the STS/TULA family recently emerged as important regulators of cellular functions. They exhibit a unique domain architecture, featuring at least three interactive/functional domains. Despite a significant degree of homology between the two members of this family, there are considerable functional differences between them. Thus, one of them is ubiquitously expressed in mammalian tissues and exhibits high phosphatase activity, whereas the other one is expressed in lymphocytes only and exhibits very low phosphatase activity, but is capable of promoting apoptosis, an activity unique for this family member. Among several functions reported for STS/TULA proteins, the most characterized one is the regulation of protein tyrosine kinase-mediated signaling. Interestingly, gene deletion of neither family member results in a discernible phenotype, whereas simultaneous deletion of both members causes hyperreactivity of T cells. Despite their apparent importance, the physiological role and the molecular basis of the effects of STS/TULA proteins remain poorly understood. This brief review summarizes what is currently known about the STS/TULA family and outlines the unresolved questions in this area.