The Sts Proteins: Modulators of Host Immunity

Anika Zaman, Jarrod B. French, Nick Carpino

Research output: Contribution to journalReview articlepeer-review


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-1HP 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-2HP is significantly lower than that of Sts-1HP, 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 (C. albicans) and a Gram-negative bacterial pathogen (F. tularensis). In particular, Sts-/- 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.

Original languageEnglish (US)
Article number8834
JournalInternational journal of molecular sciences
Issue number10
StatePublished - May 2023

Bibliographical note

Funding Information:
This research was funded by the National Institutes of Health: R01AI141592 (N.C., J.B.F.) and R21AI156238 (N.C., J.B.F.). We thank the Stony Brook University Department of Microbiology and Immunology for additional support.

Publisher Copyright:
© 2023 by the authors.


  • Candida albicans
  • Francisella tularensis
  • Sts-1
  • Sts-2
  • histidine phosphatase
  • phosphodiesterase

PubMed: MeSH publication types

  • Journal Article
  • Review


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