TULA proteins bind to ABCE-1, a host factor of HIV-1 assembly, and inhibit HIV-1 biogenesis in a UBA-dependent fashion

Smirnova, Evgeniya V.; Collingwood, Therese S.; Bisbal, Catherine; Tsygankova, Oxana M.; Bogush, Marina; Meinkoth, Judy L.; Henderson, Earl E.; Annan, Roland S.; Tsygankov, Alexander Y.

doi:10.1016/j.virol.2007.10.012

Cited by 22 publications

(21 citation statements)

References 80 publications

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“…However, it is apparent that more TULA is present in the cytosol and in the membrane than in the nucleus (5,14). Immunofluorescence staining is consistent with these results, indicating that TULA is primarily seen in the perinuclear area of the cytoplasm and that this staining demonstrates a diffuse/speckled pattern (7,8,14,15). Immunofluorescence staining of TULA-2 exhibited, likewise, the speckled/ diffuse intracellular localization of this protein in the cytoplasm (7,16).…”

Section: Protein Structure and Protein-protein Interactions Of Tulasupporting

confidence: 67%

Multidomain STS/TULA proteins are novel cellular regulators

Tsygankov

2008

IUBMB Life

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SummaryProteins 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.2008 IUBMB IUBMB Life, 60(4): [224][225][226][227][228][229][230][231] 2008

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Section: Protein Structure and Protein-protein Interactions Of Tulasupporting

confidence: 67%

Multidomain STS/TULA proteins are novel cellular regulators

Tsygankov

2008

IUBMB Life

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“…Anti-CD25/IL-2R␣ mouse monoclonal antibody was from R&D Systems (Minneapolis, MN). Anti-TULA-2 rabbit polyclonal antibody was described previously (5). Antibody to FcR␥ was purchased from Millipore (catalog no.…”

Section: Tula-2 Inhibits Syk By Dephosphorylating Tyr(p)mentioning

confidence: 99%

TULA-2 Protein Phosphatase Suppresses Activation of Syk through the GPVI Platelet Receptor for Collagen by Dephosphorylating Tyr(P)346, a Regulatory Site of Syk

Reppschläger

Gosselin²,

Dangelmaier

et al. 2016

Journal of Biological Chemistry

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Protein-tyrosine phosphatase TULA-2 has been shown to regulate receptor signaling in several cell types, including platelets. Platelets are critical for maintaining vascular integrity; this function is mediated by platelet aggregation in response to recognition of the exposed basement membrane collagen by the GPVI receptor, which is non-covalently associated with the signal-transducing FcR␥ polypeptide chain. Our previous studies suggested that TULA-2 plays an important role in negatively regulating signaling through GPVI-FcR␥ and indicated that the tyrosine-protein kinase Syk is a key target of the regulatory action of TULA-2 in platelets. However, the molecular basis of the down-regulatory effect of TULA-2 on Syk activation via FcR␥ remained unclear. In this study, we demonstrate that suppression of Syk activation by TULA-2 is mediated, to a substantial degree, by dephosphorylation of Tyr(P) 346 , a regulatory site of Syk, which becomes phosphorylated soon after receptor ligation and plays a critical role in initiating the process that yields fully activated Syk. TULA-2 is capable of dephosphorylating Tyr(P) 346 with high efficiency, thus controlling the overall activation of Syk, but is less efficient in dephosphorylating other regulatory sites of this kinase. Therefore, dephosphorylation of Tyr(P) 346 may be considered an important "checkpoint" in the regulation of Syk activation process. Putative biological functions of TULA-2-mediated dephosphorylation of Tyr(P) 346 may include deactivation of receptor-activated Syk or suppression of Syk activation by suboptimal stimulation.Proteins of the two-member UBASH3/STS/TULA family featuring the histidine phosphatase domain in their structure act as regulators of signaling and other cellular processes in several experimental systems (1-11) (reviewed in Refs. 12-14).TULA-2, also termed p70, STS-1, or UBASH3B, has been shown to be an active protein-tyrosine phosphatase (PTP) 2 (15-17) capable of suppressing receptor signaling in T lymphocytes (1, 7, 9, 15), mast cells (18), osteoclasts (8), and platelets (6,19,20).Platelets play a key role in maintaining vascular integrity. Platelets circulate in the bloodstream in a quiescent discoid shape until they interact with collagen, an essential part of the extracellular matrix, which becomes exposed upon blood vessel injury. This interaction triggers signaling, which activates platelets and causes their aggregation, thus developing a plug to arrest bleeding (21, 22). However, this trigger-like response can also have deleterious consequences if left unchecked. Therefore, negative regulation of platelet signaling is critical for maintaining a balance between hemostasis and thrombosis (23).Our previous studies suggested that TULA-2 plays an important role in negatively regulating platelet signaling through GPVI, a receptor for collagen non-covalently associated with Fc⑀R1␥ (denoted FcR␥ throughout), and Fc␥RIIA, an IgG Fc receptor, both of which transmit signals through the immunoreceptor tyrosine-based activation motifs (ITA...

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“…However, phosphorylation of this site is largely constitutive under conditions of our experiments and, thus, may be regulated quite differently from the other sites studied. Another possible reason for the observed discrepancies might be the contribution of the N-terminal ubiquitin-association and Src homology 3 domains, which mediate protein-protein interactions (4,5,7,11,12,(33)(34)(35)(36). These protein binding domains may target the catalytic domain of TULA-2 to specific protein substrates (e.g.…”

Section: Discussionmentioning

confidence: 99%

“…TULA-1 and TULA-2 have been shown to play a role in regulating receptor-mediated signaling in T cells (3,6) as well as other signaling pathways (4,5,11,12). Interestingly, despite their similarity in protein sequence and structure, TULA-1 and TULA-2 have very different cellular functions.…”

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confidence: 99%

Determination of the Substrate Specificity of Protein-tyrosine Phosphatase TULA-2 and Identification of Syk as a TULA-2 Substrate

Chen

Ren

Kim

et al. 2010

Journal of Biological Chemistry

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TULA-1 (UBASH3A/STS-2) and TULA-2 (p70/STS-1) represent a novel class of protein-tyrosine phosphatases. Previous studies suggest that TULA-2 is sequence-selective toward phosphotyrosyl (Tyr(P)) peptides. In this work the substrate specificity of TULA-1 and -2 was systematically evaluated by screening a combinatorial Tyr(P) peptide library. Although TULA-1 showed no detectable activity toward any of the Tyr(P) peptides in the library, TULA-2 recognizes two distinct classes of Tyr(P) substrates. On the N-terminal side of Tyr(P), the class I substrates contain a proline at the Tyr(P)؊1 position, a hydrophilic residue at the Tyr(P)؊2 position, and aromatic hydrophobic residues at positions Tyr(P)؊3 and beyond. The class II substrates typically contain two or more acidic residues, especially at Tyr(P)؊1 to Tyr(P)؊3 positions, and aromatic hydrophobic residues at other positions. At the C-terminal side of Tyr(P), TULA-2 generally prefers acidic and aromatic residues. The library screening results were confirmed by kinetic analysis of representative peptides selected from the library as well as Tyr(P) peptides derived from various Tyr(P) proteins. TULA-2 is highly active toward peptides corresponding to the Tyr(P)-323 and Tyr(P)-352 sites of Syk, and the Tyr(P)-397 site of focal adhesion kinase and has lower activity toward other Tyr(P) sites in these proteins. In glycoprotein VI-stimulated platelets, knock-out of the TULA-2 gene significantly increased the phosphorylation level of Syk at Tyr-323 and Tyr-352 sites and to a lesser degree at the Tyr-525/526 sites. These results suggest that Syk is a bona fide TULA-2 substrate in platelets.

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TULA proteins bind to ABCE-1, a host factor of HIV-1 assembly, and inhibit HIV-1 biogenesis in a UBA-dependent fashion

Cited by 22 publications

References 80 publications

Multidomain STS/TULA proteins are novel cellular regulators

Multidomain STS/TULA proteins are novel cellular regulators

TULA-2 Protein Phosphatase Suppresses Activation of Syk through the GPVI Platelet Receptor for Collagen by Dephosphorylating Tyr(P)346, a Regulatory Site of Syk

Determination of the Substrate Specificity of Protein-tyrosine Phosphatase TULA-2 and Identification of Syk as a TULA-2 Substrate

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