LYP Regulates SLP76 and Other Adaptor Proteins in T Cells

Overview

Journal Biol Res

Specialty Biology

Date 2024 Sep 28

PMID 39342392

Authors

Virginia Ruiz-Martin

Tamara Marcos

Jose Maria de Pereda

Mariano Sanchez-Crespo

Miguel Angel de la Fuente

Yolanda Bayon

Andres Alonso

Affiliations

Soon will be listed here.

Abstract

Background: The LYP tyrosine phosphatase presents a SNP (1858C > T) that increases the risk of developing autoimmune diseases such as type I diabetes and arthritis. It remains unclear how this SNP affects LYP function and promotes the development of these diseases. The scarce information about LYP substrates is in part responsible for the poor understanding of LYP function.

Results: In this study, we identify in T lymphocytes several adaptor proteins as potential substrates targeted by LYP, including FYB, SLP-76, HS-1, Vav, SKAP1 and SKAP2. We also show that LYP co-localizes with SLP76 in microclusters, upon TCR engagement.

Conclusions: These data indicate that LYP may modulate T cell activation by dephosphorylating several adaptor proteins, such as FYB, SLP-76, HS-1, Vav, SKAP1 and SKAP2 upon TCR engagement.

References

Barreira M, Fabbiano S, Couceiro J, Torreira E, Martinez-Torrecuadrada J, Montoya G . The C-terminal SH3 domain contributes to the intramolecular inhibition of Vav family proteins. Sci Signal. 2014; 7(321):ra35. DOI: 10.1126/scisignal.2004993. View

Jordan M, Koretzky G . Coordination of receptor signaling in multiple hematopoietic cell lineages by the adaptor protein SLP-76. Cold Spring Harb Perspect Biol. 2010; 2(4):a002501. PMC: 2845197. DOI: 10.1101/cshperspect.a002501. View

Koretzky G, Abtahian F, Silverman M . SLP76 and SLP65: complex regulation of signalling in lymphocytes and beyond. Nat Rev Immunol. 2006; 6(1):67-78. DOI: 10.1038/nri1750. View

Acuto O, Di Bartolo V, Michel F . Tailoring T-cell receptor signals by proximal negative feedback mechanisms. Nat Rev Immunol. 2008; 8(9):699-712. DOI: 10.1038/nri2397. View

Bubeck Wardenburg J, Fu C, Jackman J, Flotow H, Wilkinson S, Williams D . Phosphorylation of SLP-76 by the ZAP-70 protein-tyrosine kinase is required for T-cell receptor function. J Biol Chem. 1996; 271(33):19641-4. DOI: 10.1074/jbc.271.33.19641. View

Singer A, Bunnell S, Obstfeld A, Jordan M, Wu J, Myung P . Roles of the proline-rich domain in SLP-76 subcellular localization and T cell function. J Biol Chem. 2004; 279(15):15481-90. DOI: 10.1074/jbc.M313339200. View

Marcos T, Ruiz-Martin V, de la Puerta M, Trinidad A, Rodriguez M, de la Fuente M . Proline-serine-threonine phosphatase interacting protein 1 inhibition of T-cell receptor signaling depends on its SH3 domain. FEBS J. 2014; 281(17):3844-54. DOI: 10.1111/febs.12912. View

Kingston R, Chen C, Rose J . Calcium phosphate transfection. Curr Protoc Mol Biol. 2008; Chapter 9:Unit 9.1. DOI: 10.1002/0471142727.mb0901s63. View

Wang Y, Shaked I, Stanford S, Zhou W, Curtsinger J, Mikulski Z . The autoimmunity-associated gene PTPN22 potentiates toll-like receptor-driven, type 1 interferon-dependent immunity. Immunity. 2013; 39(1):111-22. PMC: 3830738. DOI: 10.1016/j.immuni.2013.06.013. View

10.

Badour K, Zhang J, Shi F, Leng Y, Collins M, Siminovitch K . Fyn and PTP-PEST-mediated regulation of Wiskott-Aldrich syndrome protein (WASp) tyrosine phosphorylation is required for coupling T cell antigen receptor engagement to WASp effector function and T cell activation. J Exp Med. 2004; 199(1):99-112. PMC: 1887720. DOI: 10.1084/jem.20030976. View

11.

Stanford S, Krishnamurthy D, Falk M, Messina R, Debnath B, Li S . Discovery of a novel series of inhibitors of lymphoid tyrosine phosphatase with activity in human T cells. J Med Chem. 2011; 54(6):1640-54. PMC: 3086468. DOI: 10.1021/jm101202j. View

12.

Holzinger D, Roth J . Alarming consequences - autoinflammatory disease spectrum due to mutations in proline-serine-threonine phosphatase-interacting protein 1. Curr Opin Rheumatol. 2016; 28(5):550-9. DOI: 10.1097/BOR.0000000000000314. View

13.

Spalinger M, Kasper S, Gottier C, Lang S, Atrott K, Vavricka S . NLRP3 tyrosine phosphorylation is controlled by protein tyrosine phosphatase PTPN22. J Clin Invest. 2016; 126(5):1783-800. PMC: 4855944. DOI: 10.1172/JCI83669. View

14.

Coussens N, Hayashi R, Brown P, Balagopalan L, Balbo A, Akpan I . Multipoint binding of the SLP-76 SH2 domain to ADAP is critical for oligomerization of SLP-76 signaling complexes in stimulated T cells. Mol Cell Biol. 2013; 33(21):4140-51. PMC: 3811887. DOI: 10.1128/MCB.00410-13. View

15.

Ayoub E, Hall A, Scott A, Chagnon M, Miquel G, Halle M . Regulation of the Src kinase-associated phosphoprotein 55 homologue by the protein tyrosine phosphatase PTP-PEST in the control of cell motility. J Biol Chem. 2013; 288(36):25739-25748. PMC: 3764781. DOI: 10.1074/jbc.M113.501007. View

16.

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

17.

Arechiga A, Habib T, He Y, Zhang X, Zhang Z, Funk A . Cutting edge: the PTPN22 allelic variant associated with autoimmunity impairs B cell signaling. J Immunol. 2009; 182(6):3343-7. PMC: 2797545. DOI: 10.4049/jimmunol.0713370. View

18.

Hornbeck P, Zhang B, Murray B, Kornhauser J, Latham V, Skrzypek E . PhosphoSitePlus, 2014: mutations, PTMs and recalibrations. Nucleic Acids Res. 2014; 43(Database issue):D512-20. PMC: 4383998. DOI: 10.1093/nar/gku1267. View

19.

Geng L, Raab M, Rudd C . Cutting edge: SLP-76 cooperativity with FYB/FYN-T in the Up-regulation of TCR-driven IL-2 transcription requires SLP-76 binding to FYB at Tyr595 and Tyr651. J Immunol. 1999; 163(11):5753-7. View

20.

Cloutier J, Veillette A . Cooperative inhibition of T-cell antigen receptor signaling by a complex between a kinase and a phosphatase. J Exp Med. 1999; 189(1):111-21. PMC: 1887684. DOI: 10.1084/jem.189.1.111. View