A Phosphatase Activity of Sts-1 Contributes to the Suppression of TCR Signaling

Overview

Journal Mol Cell

Publisher Cell Press

Specialty Cell Biology

Date 2007 Aug 7

PMID 17679096

Citations 69

Authors

Anatoly Mikhailik

Bradley Ford

James Keller

Yunting Chen

Nicolas Nassar

Nick Carpino

Affiliations

Soon will be listed here.

Abstract

Precise signaling by the T cell receptor (TCR) is crucial for a proper immune response. To ensure that T cells respond appropriately to antigenic stimuli, TCR signaling pathways are subject to multiple levels of regulation. Sts-1 negatively regulates signaling pathways downstream of the TCR by an unknown mechanism(s). Here, we demonstrate that Sts-1 is a phosphatase that can target the tyrosine kinase Zap-70 among other proteins. The X-ray structure of the Sts-1 C terminus reveals that it has homology to members of the phosphoglycerate mutase/acid phosphatase (PGM/AcP) family of enzymes, with residues known to be important for PGM/AcP catalytic activity conserved in nature and position in Sts-1. Point mutations that impair Sts-1 phosphatase activity in vitro also impair the ability of Sts-1 to regulate TCR signaling in T cells. These observations reveal a PGM/AcP-like enzyme activity involved in the control of antigen receptor signaling.

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References

Kowanetz K, Crosetto N, Haglund K, Schmidt M, Heldin C, Dikic I . Suppressors of T-cell receptor signaling Sts-1 and Sts-2 bind to Cbl and inhibit endocytosis of receptor tyrosine kinases. J Biol Chem. 2004; 279(31):32786-95. DOI: 10.1074/jbc.M403759200. View

Winn S, Watson H, Harkins R, Fothergill L . Structure and activity of phosphoglycerate mutase. Philos Trans R Soc Lond B Biol Sci. 1981; 293(1063):121-30. DOI: 10.1098/rstb.1981.0066. View

Bazan J, Fletterick R, Pilkis S . Evolution of a bifunctional enzyme: 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase. Proc Natl Acad Sci U S A. 1989; 86(24):9642-6. PMC: 298557. DOI: 10.1073/pnas.86.24.9642. View

Vincent J, Crowder M, Averill B . Hydrolysis of phosphate monoesters: a biological problem with multiple chemical solutions. Trends Biochem Sci. 1992; 17(3):105-10. DOI: 10.1016/0968-0004(92)90246-6. View

Lee Y, Ogata C, Pflugrath J, Levitt D, Sarma R, BANASZAK L . Crystal structure of the rat liver fructose-2,6-bisphosphatase based on selenomethionine multiwavelength anomalous dispersion phases. Biochemistry. 1996; 35(19):6010-9. DOI: 10.1021/bi9600613. View

Cheng A, Negishi I, Anderson S, Chan A, Bolen J, Loh D . The Syk and ZAP-70 SH2-containing tyrosine kinases are implicated in pre-T cell receptor signaling. Proc Natl Acad Sci U S A. 1997; 94(18):9797-801. PMC: 23271. DOI: 10.1073/pnas.94.18.9797. View

Meng T, Lin M . Tyrosine phosphorylation of c-ErbB-2 is regulated by the cellular form of prostatic acid phosphatase in human prostate cancer cells. J Biol Chem. 1998; 273(34):22096-104. DOI: 10.1074/jbc.273.34.22096. View

Moriggl R, Topham D, Teglund S, Sexl V, Mckay C, Wang D . Stat5 is required for IL-2-induced cell cycle progression of peripheral T cells. Immunity. 1999; 10(2):249-59. DOI: 10.1016/s1074-7613(00)80025-4. View

KILSHEIMER G, AXELROD B . Inhibition of prostatic acid phosphatase by alpha-hydroxycarboxylic acids. J Biol Chem. 1957; 227(2):879-90. View

10.

Mustelin T, Vang T, Bottini N . Protein tyrosine phosphatases and the immune response. Nat Rev Immunol. 2005; 5(1):43-57. DOI: 10.1038/nri1530. View

11.

Wiedemann A, Muller S, Favier B, Penna D, Guiraud M, Delmas C . T-cell activation is accompanied by an ubiquitination process occurring at the immunological synapse. Immunol Lett. 2005; 98(1):57-61. DOI: 10.1016/j.imlet.2004.10.014. View

12.

Ohno A, Jee J, Fujiwara K, Tenno T, Goda N, Tochio H . Structure of the UBA domain of Dsk2p in complex with ubiquitin molecular determinants for ubiquitin recognition. Structure. 2005; 13(4):521-32. DOI: 10.1016/j.str.2005.01.011. View

13.

Hicke L, Schubert H, Hill C . Ubiquitin-binding domains. Nat Rev Mol Cell Biol. 2005; 6(8):610-21. DOI: 10.1038/nrm1701. View

14.

Feshchenko E, Smirnova E, Swaminathan G, Teckchandani A, Agrawal R, Band H . TULA: an SH3- and UBA-containing protein that binds to c-Cbl and ubiquitin. Oncogene. 2004; 23(27):4690-706. DOI: 10.1038/sj.onc.1207627. View

15.

Kleinman H, Ford B, Keller J, Carpino N, Nassar N . Crystallization and initial crystal characterization of the C-terminal phosphoglycerate mutase homology domain of Sts-1. Acta Crystallogr Sect F Struct Biol Cryst Commun. 2006; 62(Pt 3):218-20. PMC: 2197191. DOI: 10.1107/S1744309106003320. View

16.

Brunger A . Free R value: a novel statistical quantity for assessing the accuracy of crystal structures. Nature. 1992; 355(6359):472-5. DOI: 10.1038/355472a0. View

17.

Jakob C, Lewinski K, Kuciel R, OSTROWSKI W, Lebioda L . Crystal structure of human prostatic acid phosphatase . Prostate. 2000; 42(3):211-8. DOI: 10.1002/(sici)1097-0045(20000215)42:3<211::aid-pros7>3.0.co;2-u. View

18.

Jedrzejas M . Structure, function, and evolution of phosphoglycerate mutases: comparison with fructose-2,6-bisphosphatase, acid phosphatase, and alkaline phosphatase. Prog Biophys Mol Biol. 2000; 73(2-4):263-87. DOI: 10.1016/s0079-6107(00)00007-9. View

19.

Wattenhofer M, Shibuya K, Kudoh J, Lyle R, Michaud J, Rossier C . Isolation and characterization of the UBASH3A gene on 21q22.3 encoding a potential nuclear protein with a novel combination of domains. Hum Genet. 2001; 108(2):140-7. DOI: 10.1007/s004390000453. View

20.

Bond C, White M, Hunter W . High resolution structure of the phosphohistidine-activated form of Escherichia coli cofactor-dependent phosphoglycerate mutase. J Biol Chem. 2000; 276(5):3247-53. DOI: 10.1074/jbc.M007318200. View