Molecular Mechanisms Underlying the Evolution of the Slp76 Signalosome

Overview

Journal Sci Rep

Specialty Science

Date 2017 May 6

PMID 28473706

Citations 2

Authors

Xuemei Qu

Xin Lan

Chong Deng

Jiatao Zhou

Jingjing Du

Shengfeng Huang

Yingqiu Li

Affiliations

Soon will be listed here.

Abstract

The well-defined mammalian slp76-signalosome is crucial for T-cell immune response, yet whether slp76-signalosome exists in invertebrates and how it evolved remain unknown. Here we investigated slp76-signalosome from an evolutionary perspective in amphioxus Branchiostoma belcheri (bb). We proved slp76-signalosome components bbslp76, bbGADS and bbItk are present in amphioxus and bbslp76 interacts with bbGADS and bbItk, but differences exist between the interaction manners within slp76-signalosome components of amphioxus and human (h). Specifically, bbslp76 has a unique WW-domain that blocked its association with hItk and decreased TCR-induced tyrosine-phosphorylation and NFAT-activation. Deletion of WW-domain shifted the constitutive association between bbslp76 and hPLCγ1 to a TCR-enhanced association. Among slp76-signalosome, the interaction between slp76 and PLCγ1 is the most conserved and the binding between Itk and slp76 evolved from constitutive to stimulation-regulated. Sequence alignment and 3D structural analysis of slp76-signalosome molecules from keystone species indicated slp76 evolved into a more unfolded and flexible adaptor due to lack of WW-domain and several low-complexity-regions (LCRs) while GADS turned into a larger protein by a LCR gain, thus preparing more space for nucleating the coevolving slp76-signalosome. Altogether, through deletion of WW-domain and manipulation of LCRs, slp76-signalosome evolves from a rigid and stimulation-insensitive to a more flexible and stimulation-responding complex.

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References

Pennisi E . Genetics. Sea urchin genome confirms kinship to humans and other vertebrates. Science. 2006; 314(5801):908-9. DOI: 10.1126/science.314.5801.908. View

Asada H, Ishii N, Sasaki Y, Endo K, Kasai H, Tanaka N . Grf40, A novel Grb2 family member, is involved in T cell signaling through interaction with SLP-76 and LAT. J Exp Med. 1999; 189(9):1383-90. PMC: 2193052. DOI: 10.1084/jem.189.9.1383. 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

Xie J, Liang J, Diao L, Altman A, Li Y . TNFR-associated factor 6 regulates TCR signaling via interaction with and modification of LAT adapter. J Immunol. 2013; 190(8):4027-36. PMC: 3622165. DOI: 10.4049/jimmunol.1202742. View

Yablonski D, Kadlecek T, Weiss A . Identification of a phospholipase C-gamma1 (PLC-gamma1) SH3 domain-binding site in SLP-76 required for T-cell receptor-mediated activation of PLC-gamma1 and NFAT. Mol Cell Biol. 2001; 21(13):4208-18. PMC: 87082. DOI: 10.1128/MCB.21.13.4208-4218.2001. View

Devkota S, Joseph R, Min L, Fulton D, Andreotti A . Scaffold Protein SLP-76 Primes PLCγ1 for Activation by ITK-Mediated Phosphorylation. J Mol Biol. 2015; 427(17):2734-47. PMC: 4540666. DOI: 10.1016/j.jmb.2015.04.012. View

Sela M, Bogin Y, Beach D, Oellerich T, Lehne J, Smith-Garvin J . Sequential phosphorylation of SLP-76 at tyrosine 173 is required for activation of T and mast cells. EMBO J. 2011; 30(15):3160-72. PMC: 3160187. DOI: 10.1038/emboj.2011.213. View

Kanner S . Regulated association between the tyrosine kinase Emt/Itk/Tsk and phospholipase-C gamma 1 in human T lymphocytes. J Immunol. 1999; 163(12):6435-41. View

Liu S, Fang N, Koretzky G, McGlade C . The hematopoietic-specific adaptor protein gads functions in T-cell signaling via interactions with the SLP-76 and LAT adaptors. Curr Biol. 1999; 9(2):67-75. DOI: 10.1016/s0960-9822(99)80017-7. View

10.

Cao D, Liao X, Cheng W, Jiang Y, Wang W, Li Q . Structure of a variable lymphocyte receptor-like protein from the amphioxus Branchiostoma floridae. Sci Rep. 2016; 6:19951. PMC: 4731796. DOI: 10.1038/srep19951. View

11.

Bubeck Wardenburg J, Pappu R, Bu J, Mayer B, Chernoff J, Straus D . Regulation of PAK activation and the T cell cytoskeleton by the linker protein SLP-76. Immunity. 1998; 9(5):607-16. DOI: 10.1016/s1074-7613(00)80658-5. View

12.

Ilsley J, Sudol M, Winder S . The WW domain: linking cell signalling to the membrane cytoskeleton. Cell Signal. 2002; 14(3):183-9. DOI: 10.1016/s0898-6568(01)00236-4. View

13.

Balagopalan L, Coussens N, Sherman E, Samelson L, Sommers C . The LAT story: a tale of cooperativity, coordination, and choreography. Cold Spring Harb Perspect Biol. 2010; 2(8):a005512. PMC: 2908767. DOI: 10.1101/cshperspect.a005512. View

14.

Yokosuka T, Sakata-Sogawa K, Kobayashi W, Hiroshima M, Hashimoto-Tane A, Tokunaga M . Newly generated T cell receptor microclusters initiate and sustain T cell activation by recruitment of Zap70 and SLP-76. Nat Immunol. 2005; 6(12):1253-62. DOI: 10.1038/ni1272. View

15.

Raab M, da Silva A, Findell P, Rudd C . Regulation of Vav-SLP-76 binding by ZAP-70 and its relevance to TCR zeta/CD3 induction of interleukin-2. Immunity. 1997; 6(2):155-64. DOI: 10.1016/s1074-7613(00)80422-7. View

16.

Fang N, Motto D, Ross S, Koretzky G . Tyrosines 113, 128, and 145 of SLP-76 are required for optimal augmentation of NFAT promoter activity. J Immunol. 1996; 157(9):3769-73. View

17.

Brownlie R, Zamoyska R . T cell receptor signalling networks: branched, diversified and bounded. Nat Rev Immunol. 2013; 13(4):257-69. DOI: 10.1038/nri3403. View

18.

Mingueneau M, Roncagalli R, Gregoire C, Kissenpfennig A, Miazek A, Archambaud C . Loss of the LAT adaptor converts antigen-responsive T cells into pathogenic effectors that function independently of the T cell receptor. Immunity. 2009; 31(2):197-208. DOI: 10.1016/j.immuni.2009.05.013. View

19.

Bogin Y, Ainey C, Beach D, Yablonski D . SLP-76 mediates and maintains activation of the Tec family kinase ITK via the T cell antigen receptor-induced association between SLP-76 and ITK. Proc Natl Acad Sci U S A. 2007; 104(16):6638-43. PMC: 1871838. DOI: 10.1073/pnas.0609771104. View

20.

Zhang W, Trible R, Zhu M, Liu S, McGlade C, Samelson L . Association of Grb2, Gads, and phospholipase C-gamma 1 with phosphorylated LAT tyrosine residues. Effect of LAT tyrosine mutations on T cell angigen receptor-mediated signaling. J Biol Chem. 2000; 275(30):23355-61. DOI: 10.1074/jbc.M000404200. View