TULA‐family proteins: A new class of cellular regulators

Proteins of the UBASH3/STS/TULA family recently emerged as potent regulators of cellular functions. They are characterized by a unique architecture, featuring at least three functional domains. One of them is a histidine phosphatase domain, which mediates the protein tyrosine phosphatase activity of these proteins. Recent studies demonstrated that UBASH3/STS/TULA‐family proteins play a key role in down‐regulating receptor‐mediated signal transduction and physiologic responses of T cells and platelets in vitro and in vivo. The Syk‐family protein tyrosine kinases Syk and Zap‐70 were identified as major targets of TULA‐2 in full agreement with the suppressive effect of this phosphatase in systems where Syk and Zap‐70 carry out the essential early steps of signal transduction. In spite of significant similarity between TULA and TULA‐2, there are also considerable functional differences between them. Thus, TULA‐2 is expressed ubiquitously in mammalian tissues and exhibits high phosphatase activity, whereas TULA is expressed specifically in lymphocytes and exhibits low phosphatase activity. However, TULA also functions as a down‐regulator of cellular responses, and therefore its role may be mediated by dephosphorylation of yet‐unknown substrates or by promoting T‐cell apoptosis (the latter activity is unique for this UBASH3/STS/TULA family member). The down‐regulatory role of TULA and TULA‐2 revealed in experimental systems is consistent with the recently discovered association of several autoimmune diseases with certain risk alleles encoding for these proteins. J. Cell. Physiol. 228: 43–49, 2013. © 2012 Wiley Periodicals, Inc.