TULA Proteins in Men, Mice, Hens, and Lice: Welcome to the Family

Abstract

The two members of the UBASH3/STS/TULA protein family have been shown to critically regulate key biological functions, including immunity and hemostasis, in mammalian biological systems. Negative regulation of signaling through immune receptor tyrosine-based activation motif (ITAM)- and hemITAM-bearing receptors mediated by Syk-family protein tyrosine kinases appears to be a major molecular mechanism of the down-regulatory effect of TULA-family proteins, which possess protein tyrosine phosphatase (PTP) activity. However, these proteins are likely to carry out some PTP-independent functions as well. Whereas the effects of TULA-family proteins overlap, their characteristics and their individual contributions to cellular regulation also demonstrate clearly distinct features. Protein structure, enzymatic activity, molecular mechanisms of regulation, and biological functions of TULA-family proteins are discussed in this review. In particular, the usefulness of the comparative analysis of TULA proteins in various metazoan taxa, for identifying potential roles of TULA-family proteins outside of their functions already established in mammalian systems, is examined.

Role of Tula-Family Proteins in Cell Signaling and Activation: Advances and Challenges

“…However, this comparative analysis identifies atypical taxa as well; UBASH3A appears to be lost at the root of the ray-finned fish tree; thus, some ray-finned fish species thrive possessing only a single family member. Further analysis suggests that the loss of UBASH3A is followed by the formation of a unique UBASH3 family in teleosts, which possess two or even three UBASH3B-related loci [33]. This atypical UBASH3 family differs dramatically from its conserved form found in most vertebrates, although the immune system of teleosts is similar to that of other vertebrates, including mammals [34][35][36], in which both UBASH3A and UBASH3B play important and, to a substantial extent, specific roles.…”

“…This analysis indicates that the presence of a UBASH3-like gene is typical for all invertebrates, while the two-member UBASH3 family is typical for vertebrate species. This family is highly conserved in such diverse taxa as mammals and other tetrapods, lobefinned fish, which are considered 'living fossils', and sharks [33]. These findings imply that the systems specific to vertebrates, including adaptive immunity with its lymphocytes and the closed circulatory system with its thrombocytes and platelets, require this two-member family instead of a single protein for building the respective regulatory circuits.…”

“…The effects of UBASH3A/B on cell signaling and responses are also reviewed by Tsygankov [33]. In addition to the effects of both family members on immune cells, the effects of UBASH3B on platelets, which appear to play an important role in the regulation of hemostasis and thrombosis [13,29], are discussed.…”

FLI1 induces erythroleukemia through opposing effects on UBASH3A and UBASH3B expression

“…UBASH3A (STS-2/TULA/ CLIP4) and UBASH3B (STS-1/TULA-2) belong to the ubiquitin-associated and Src-homology 3 domain-containing (UBASH3) family [ 1 ]. While UBASH3B is ubiquitously expressed [ 2 ], UBASH3A expression is restricted to lymphoid tissues [ 3 ].…”

The Ubiquitin-Associated and SH3 Domain-Containing Proteins (UBASH3) Family in Mammalian Development and Immune Response

“…The UBASH3 family, specifically UBASH3A (previously known as Sts-1) and UBASH3B (previously known as Sts-2), plays crucial roles during mammalian development and immune responses [1]. These proteins contain ubiquitin-associated (UBA) and Src homology 3 (SH3) domains, which are essential for their functions in cellular signalling, particularly in regulating immune cell signalling [2].…”