The Sts Proteins: Modulators of Host Immunity
The suppressor of TCR signaling (Sts) proteins, Sts-1 and Sts-2, are a pair of closely related signaling molecules that belong to the histidine phosphatase (HP) family of enzymes by virtue of an evolutionarily conserved C-terminal phosphatase domain. HPs derive their name from a conserved histidine...
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MDPI AG
2023-05-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/24/10/8834 |
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| author | Anika Zaman Jarrod B. French Nick Carpino |
| author_facet | Anika Zaman Jarrod B. French Nick Carpino |
| author_sort | Anika Zaman |
| collection | DOAJ |
| description | The suppressor of TCR signaling (Sts) proteins, Sts-1 and Sts-2, are a pair of closely related signaling molecules that belong to the histidine phosphatase (HP) family of enzymes by virtue of an evolutionarily conserved C-terminal phosphatase domain. HPs derive their name from a conserved histidine that is important for catalytic activity and the current evidence indicates that the Sts HP domain plays a critical functional role. Sts-1<sub>HP</sub> has been shown to possess a readily measurable protein tyrosine phosphatase activity that regulates a number of important tyrosine-kinase-mediated signaling pathways. The in vitro catalytic activity of Sts-2<sub>HP</sub> is significantly lower than that of Sts-1<sub>HP</sub>, and its signaling role is less characterized. The highly conserved unique structure of the Sts proteins, in which additional domains, including one that exhibits a novel phosphodiesterase activity, are juxtaposed together with the phosphatase domain, suggesting that Sts-1 and -2 occupy a specialized intracellular signaling niche. To date, the analysis of Sts function has centered predominately around the role of Sts-1 and -2 in regulating host immunity and other responses associated with cells of hematopoietic origin. This includes their negative regulatory role in T cells, platelets, mast cells and other cell types, as well as their less defined roles in regulating host responses to microbial infection. Regarding the latter, the use of a mouse model lacking Sts expression has been used to demonstrate that Sts contributes non-redundantly to the regulation of host immunity toward a fungal pathogen (<i>C. albicans</i>) and a Gram-negative bacterial pathogen (<i>F. tularensis</i>). In particular, <i>Sts</i>-/- animals demonstrate significant resistance to lethal infections of both pathogens, a phenotype that is correlated with some heightened anti-microbial responses of phagocytes derived from mutant mice. Altogether, the past several years have seen steady progress in our understanding of Sts biology. |
| first_indexed | 2024-03-11T03:39:10Z |
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| language | English |
| last_indexed | 2024-03-11T03:39:10Z |
| publishDate | 2023-05-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | International Journal of Molecular Sciences |
| spelling | doaj.art-04095c993d05415c816bf0ce0914dbf62023-11-18T01:42:47ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672023-05-012410883410.3390/ijms24108834The Sts Proteins: Modulators of Host ImmunityAnika Zaman0Jarrod B. French1Nick Carpino2Graduate Program in Molecular and Cellular Pharmacology, Stony Brook University, Stony Brook, NY 11794, USAHormel Institute, University of Minnesota, 801 16th Ave NE, Austin, MN 55912, USADepartment of Microbiology and Immunology, Stony Brook University, Stony Brook, NY 11794, USAThe suppressor of TCR signaling (Sts) proteins, Sts-1 and Sts-2, are a pair of closely related signaling molecules that belong to the histidine phosphatase (HP) family of enzymes by virtue of an evolutionarily conserved C-terminal phosphatase domain. HPs derive their name from a conserved histidine that is important for catalytic activity and the current evidence indicates that the Sts HP domain plays a critical functional role. Sts-1<sub>HP</sub> has been shown to possess a readily measurable protein tyrosine phosphatase activity that regulates a number of important tyrosine-kinase-mediated signaling pathways. The in vitro catalytic activity of Sts-2<sub>HP</sub> is significantly lower than that of Sts-1<sub>HP</sub>, and its signaling role is less characterized. The highly conserved unique structure of the Sts proteins, in which additional domains, including one that exhibits a novel phosphodiesterase activity, are juxtaposed together with the phosphatase domain, suggesting that Sts-1 and -2 occupy a specialized intracellular signaling niche. To date, the analysis of Sts function has centered predominately around the role of Sts-1 and -2 in regulating host immunity and other responses associated with cells of hematopoietic origin. This includes their negative regulatory role in T cells, platelets, mast cells and other cell types, as well as their less defined roles in regulating host responses to microbial infection. Regarding the latter, the use of a mouse model lacking Sts expression has been used to demonstrate that Sts contributes non-redundantly to the regulation of host immunity toward a fungal pathogen (<i>C. albicans</i>) and a Gram-negative bacterial pathogen (<i>F. tularensis</i>). In particular, <i>Sts</i>-/- animals demonstrate significant resistance to lethal infections of both pathogens, a phenotype that is correlated with some heightened anti-microbial responses of phagocytes derived from mutant mice. Altogether, the past several years have seen steady progress in our understanding of Sts biology.https://www.mdpi.com/1422-0067/24/10/8834Sts-1Sts-2histidine phosphatasephosphodiesterase<i>Candida albicans</i><i>Francisella tularensis</i> |
| spellingShingle | Anika Zaman Jarrod B. French Nick Carpino The Sts Proteins: Modulators of Host Immunity International Journal of Molecular Sciences Sts-1 Sts-2 histidine phosphatase phosphodiesterase <i>Candida albicans</i> <i>Francisella tularensis</i> |
| title | The Sts Proteins: Modulators of Host Immunity |
| title_full | The Sts Proteins: Modulators of Host Immunity |
| title_fullStr | The Sts Proteins: Modulators of Host Immunity |
| title_full_unstemmed | The Sts Proteins: Modulators of Host Immunity |
| title_short | The Sts Proteins: Modulators of Host Immunity |
| title_sort | sts proteins modulators of host immunity |
| topic | Sts-1 Sts-2 histidine phosphatase phosphodiesterase <i>Candida albicans</i> <i>Francisella tularensis</i> |
| url | https://www.mdpi.com/1422-0067/24/10/8834 |
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