Protein Tyrosine Phosphatases As Wardens of STAT Signaling

Overview

Journal JAKSTAT

Date 2014 Apr 30

PMID 24778927

Citations 54

Authors

Frank-D Bohmer

Karlheinz Friedrich

Affiliations

Soon will be listed here.

Abstract

Signaling by signal transducers and activators of transcription (STATs) is controlled at many levels of the signaling cascade. Protein tyrosine phosphatases (PTPs) regulate STAT activation at several layers, including direct pSTAT dephosphorylation in both cytoplasm and nucleus. Despite the importance of this regulation mode, many aspects are still incompletely understood, e.g., the identity of PTPs acting on certain members of the STAT family. After a brief introduction into the STAT and PTP families, we discuss here the current knowledge on PTP mediated regulation of STAT activity, focusing on the interaction of individual STATs with specific PTPs. Finally, we highlight open questions and propose important tasks of future research.

Citing Articles

Targeting Fibrosis: From Molecular Mechanisms to Advanced Therapies.

Di X, Li Y, Wei J, Li T, Liao B Adv Sci (Weinh). 2024; 12(3):e2410416.

PMID: 39665319 PMC: 11744640. DOI: 10.1002/advs.202410416.

Integrative Multi-PTM Proteomics Reveals Dynamic Global, Redox, Phosphorylation, and Acetylation Regulation in Cytokine-Treated Pancreatic Beta Cells.

Gluth A, Li X, Gritsenko M, Gaffrey M, Kim D, Lalli P Mol Cell Proteomics. 2024; 23(12):100881.

PMID: 39550035 PMC: 11700301. DOI: 10.1016/j.mcpro.2024.100881.

Age-associated myeloid malignancies - the role of STAT3 and STAT5 in myelodysplastic syndrome and acute myeloid leukemia.

Fasouli E, Katsantoni E FEBS Lett. 2024; 598(22):2809-2828.

PMID: 39048534 PMC: 11586607. DOI: 10.1002/1873-3468.14985.

Upregulation of TCPTP in Macrophages Is Involved in IL-35 Mediated Attenuation of Experimental Colitis.

Zhang B, Sun C, Zhu Y, Qin H, Kong D, Zhang J Mediators Inflamm. 2024; 2024:3282679.

PMID: 38962170 PMC: 11221972. DOI: 10.1155/2024/3282679.

Latent Epstein-Barr virus infection collaborates with Myc over-expression in normal human B cells to induce Burkitt-like Lymphomas in mice.

Bristol J, Nelson S, Ohashi M, Casco A, Hayes M, Ranheim E PLoS Pathog. 2024; 20(4):e1012132.

PMID: 38620028 PMC: 11045125. DOI: 10.1371/journal.ppat.1012132.

References

Lu X, Malumbres R, Shields B, Jiang X, Sarosiek K, Natkunam Y . PTP1B is a negative regulator of interleukin 4-induced STAT6 signaling. Blood. 2008; 112(10):4098-108. PMC: 2582009. DOI: 10.1182/blood-2008-03-148726. View

Araki T, Kawata T, Williams J . Identification of the kinase that activates a nonmetazoan STAT gives insights into the evolution of phosphotyrosine-SH2 domain signaling. Proc Natl Acad Sci U S A. 2012; 109(28):E1931-7. PMC: 3396520. DOI: 10.1073/pnas.1202715109. View

Verma N, Dourlat J, Davies A, Long A, Liu W, Garbay C . STAT3-stathmin interactions control microtubule dynamics in migrating T-cells. J Biol Chem. 2009; 284(18):12349-62. PMC: 2673303. DOI: 10.1074/jbc.M807761200. View

Zhou Z, Gushiken F, Bolgiano D, Salsbery B, Aghakasiri N, Jing N . Signal transducer and activator of transcription 3 (STAT3) regulates collagen-induced platelet aggregation independently of its transcription factor activity. Circulation. 2012; 127(4):476-485. PMC: 4472638. DOI: 10.1161/CIRCULATIONAHA.112.132126. View

Lorenz U . SHP-1 and SHP-2 in T cells: two phosphatases functioning at many levels. Immunol Rev. 2009; 228(1):342-59. PMC: 2669678. DOI: 10.1111/j.1600-065X.2008.00760.x. View

Li L, Modi H, McDonald T, Rossi J, Yee J, Bhatia R . A critical role for SHP2 in STAT5 activation and growth factor-mediated proliferation, survival, and differentiation of human CD34+ cells. Blood. 2011; 118(6):1504-15. PMC: 3156043. DOI: 10.1182/blood-2010-06-288910. View

Chen Y, Wen R, Yang S, Schuman J, Zhang E, Yi T . Identification of Shp-2 as a Stat5A phosphatase. J Biol Chem. 2003; 278(19):16520-7. DOI: 10.1074/jbc.M210572200. View

Hoeve J, Ibarra-Sanchez M, Fu Y, Zhu W, Tremblay M, David M . Identification of a nuclear Stat1 protein tyrosine phosphatase. Mol Cell Biol. 2002; 22(16):5662-8. PMC: 133976. DOI: 10.1128/MCB.22.16.5662-5668.2002. View

Lim C, Cao X . Structure, function, and regulation of STAT proteins. Mol Biosyst. 2007; 2(11):536-50. DOI: 10.1039/b606246f. View

10.

den Hertog J, Ostman A, Bohmer F . Protein tyrosine phosphatases: regulatory mechanisms. FEBS J. 2008; 275(5):831-47. DOI: 10.1111/j.1742-4658.2008.06247.x. View

11.

Zhuang S . Regulation of STAT signaling by acetylation. Cell Signal. 2013; 25(9):1924-31. PMC: 4550442. DOI: 10.1016/j.cellsig.2013.05.007. View

12.

Johnson D, Pao L, Dhanji S, Murakami K, Ohashi P, Neel B . Shp1 regulates T cell homeostasis by limiting IL-4 signals. J Exp Med. 2013; 210(7):1419-31. PMC: 3698519. DOI: 10.1084/jem.20122239. View

13.

Patterson K, Brummer T, OBrien P, Daly R . Dual-specificity phosphatases: critical regulators with diverse cellular targets. Biochem J. 2009; 418(3):475-89. DOI: 10.1042/bj20082234. View

14.

Tiganis T, Bennett A . Protein tyrosine phosphatase function: the substrate perspective. Biochem J. 2007; 402(1):1-15. PMC: 1783993. DOI: 10.1042/BJ20061548. View

15.

Veeriah S, Brennan C, Meng S, Singh B, Fagin J, Solit D . The tyrosine phosphatase PTPRD is a tumor suppressor that is frequently inactivated and mutated in glioblastoma and other human cancers. Proc Natl Acad Sci U S A. 2009; 106(23):9435-40. PMC: 2687998. DOI: 10.1073/pnas.0900571106. View

16.

Yang J, Stark G . Roles of unphosphorylated STATs in signaling. Cell Res. 2008; 18(4):443-51. DOI: 10.1038/cr.2008.41. View

17.

Xiao W, Hong H, Kawakami Y, Kato Y, Wu D, Yasudo H . Tumor suppression by phospholipase C-beta3 via SHP-1-mediated dephosphorylation of Stat5. Cancer Cell. 2009; 16(2):161-71. PMC: 2744338. DOI: 10.1016/j.ccr.2009.05.018. View

18.

Myers M, Andersen J, Cheng A, Tremblay M, Horvath C, Parisien J . TYK2 and JAK2 are substrates of protein-tyrosine phosphatase 1B. J Biol Chem. 2001; 276(51):47771-4. DOI: 10.1074/jbc.C100583200. View

19.

Hendriks W, Elson A, Harroch S, Stoker A . Protein tyrosine phosphatases: functional inferences from mouse models and human diseases. FEBS J. 2008; 275(5):816-30. DOI: 10.1111/j.1742-4658.2008.06249.x. View

20.

Strehlow I, Schindler C . Amino-terminal signal transducer and activator of transcription (STAT) domains regulate nuclear translocation and STAT deactivation. J Biol Chem. 1998; 273(43):28049-56. DOI: 10.1074/jbc.273.43.28049. View