Gads

Summary

Gene Symbol: Gads
Description: GRB2-related adaptor protein 2
Alias: GRAP-2, GRB2L, GRBLG, GRID, Gads, GrbX, Grf40, GrpL, Mona, P38, GRB2-related adaptor protein 2, GRB-2-like protein, GRB-2-related monocytic adapter protein, Grb2-related adaptor downstream of Sch, adapter protein GRID, growth factor receptor-binding protein, hematopoietic cell-associated adaptor protein GrpL, monocytic adapter, monocytic adaptor
Species: mouse
Products:     Gads

Top Publications

  1. Liu S, McGlade C. Gads is a novel SH2 and SH3 domain-containing adaptor protein that binds to tyrosine-phosphorylated Shc. Oncogene. 1998;17:3073-82 pubmed
    ..Here we report the identification of Gads, a novel adaptor protein most similar to Grb2 and Grap that contains amino and carboxy terminal SH3 domains ..
  2. Dalheimer S, Zeng L, Draves K, Hassaballa A, Jiwa N, Parrish T, et al. Gads-deficient thymocytes are blocked at the transitional single positive CD4+ stage. Eur J Immunol. 2009;39:1395-404 pubmed publisher
    ..We sought to define the function of Gads during the two steps of positive selection by analyzing a Gads-deficient mouse line...
  3. Law C, Ewings M, Chaudhary P, Solow S, Yun T, Marshall A, et al. GrpL, a Grb2-related adaptor protein, interacts with SLP-76 to regulate nuclear factor of activated T cell activation. J Exp Med. 1999;189:1243-53 pubmed
    ..characterization of a novel Grb2-like adaptor molecule designated as Grb2-related protein of the lymphoid system (GrpL)...
  4. Bourette R, Arnaud S, Myles G, Blanchet J, Rohrschneider L, Mouchiroud G. Mona, a novel hematopoietic-specific adaptor interacting with the macrophage colony-stimulating factor receptor, is implicated in monocyte/macrophage development. EMBO J. 1998;17:7273-81 pubmed
    ..Using a yeast two-hybrid screen, we cloned a novel adaptor protein which we called 'Mona' for monocytic adaptor. Mona contains one SH2 domain and two SH3 domains related to the Grb2 adaptor...
  5. Yoder J, Pham C, Iizuka Y, Kanagawa O, Liu S, McGlade J, et al. Requirement for the SLP-76 adaptor GADS in T cell development. Science. 2001;291:1987-91 pubmed
    b>GADS is an adaptor protein implicated in CD3 signaling because of its ability to link SLP-76 to LAT. A GADS-deficient mouse was generated by gene targeting, and the function of GADS in T cell development and activation was examined...
  6. Judd B, Myung P, Obergfell A, Myers E, Cheng A, Watson S, et al. Differential requirement for LAT and SLP-76 in GPVI versus T cell receptor signaling. J Exp Med. 2002;195:705-17 pubmed
  7. Cho S, Velikovsky C, Swaminathan C, Houtman J, Samelson L, Mariuzza R. Structural basis for differential recognition of tyrosine-phosphorylated sites in the linker for activation of T cells (LAT) by the adaptor Gads. EMBO J. 2004;23:1441-51 pubmed
    ..Phosphorylation of LAT at multiple tyrosines creates binding sites for the adaptors Gads and Grb2, leading to nucleation of multiprotein signaling complexes...
  8. Chougule R, Cordero E, Moharram S, Pietras K, Rönnstrand L, Kazi J. Expression of GADS enhances FLT3-induced mitogenic signaling. Oncotarget. 2016;7:14112-24 pubmed publisher
    b>GADS is a member of a family of SH2 and SH3 domain-containing adaptors that functions in tyrosine kinase-mediated signaling cascades. Its expression is largely restricted to hematopoietic tissues and cell lines...
  9. Dufner A, Kisser A, Niendorf S, Basters A, Reissig S, Schönle A, et al. The ubiquitin-specific protease USP8 is critical for the development and homeostasis of T cells. Nat Immunol. 2015;16:950-60 pubmed publisher
    ..USP8 as a regulatory component of the T cell antigen receptor (TCR) signalosome that interacted with the adaptor Gads and the regulatory molecule 14-3-3β. Caspase-dependent processing of USP8 occurred after stimulation of the TCR...

More Information

Publications34

  1. Xiong J, Parker B, Yankee T. The combined loss of Gads and CD127 reveals a novel function of Gads prior to TCR? expression. Immunol Res. 2014;60:77-84 pubmed publisher
    The Gads adaptor protein is an essential component of the T cell signaling complex critical for T cell receptor-mediated calcium mobilization...
  2. Roncagalli R, Hauri S, Fiore F, Liang Y, Chen Z, Sansoni A, et al. Quantitative proteomics analysis of signalosome dynamics in primary T cells identifies the surface receptor CD6 as a Lat adaptor-independent TCR signaling hub. Nat Immunol. 2014;15:384-392 pubmed publisher
    ..Our findings provide a more complete model of TCR signaling in which CD6 constitutes a signaling hub that contributes to the diversification of TCR signaling. ..
  3. Gillis L, Berry D, Minden M, McGlade C, Barber D. Gads (Grb2-related adaptor downstream of Shc) is required for BCR-ABL-mediated lymphoid leukemia. Leukemia. 2013;27:1666-76 pubmed publisher
    ..We show that the GRB2-related adapter protein, GADS, also associates with BCR-ABL, specifically through Y177 and demonstrate that BCR-ABL-driven lymphoid disease ..
  4. Reeve J, Zou W, Liu Y, Maltzman J, Ross F, Teitelbaum S. SLP-76 couples Syk to the osteoclast cytoskeleton. J Immunol. 2009;183:1804-12 pubmed publisher
    ..Finally, c-Fms-activated Syk also exerts its OC cytoskeleton-organizing effect in a SLP-76/Vav3-dependent manner. ..
  5. Faravelli A, Dimasi N. Expression, refolding and crystallizations of the Grb2-like (GADS) C-terminal SH3 domain complexed with a SLP-76 motif peptide. Acta Crystallogr Sect F Struct Biol Cryst Commun. 2006;62:52-5 pubmed
    The Grb2-like adaptor protein GADS is composed of an N-terminal SH3 domain, an SH2 domain, a proline-rich region and a C-terminal SH3 domain...
  6. Yankee T, Draves K, Clark E. Expression and function of the adaptor protein Gads in murine B cells. Eur J Immunol. 2005;35:1184-92 pubmed
    ..The Gads adaptor protein is expressed in many hematopoietic tissues, including bone marrow, lymph node, and spleen...
  7. Lewitzky M, Harkiolaki M, Domart M, Jones E, Feller S. Mona/Gads SH3C binding to hematopoietic progenitor kinase 1 (HPK1) combines an atypical SH3 binding motif, R/KXXK, with a classical PXXP motif embedded in a polyproline type II (PPII) helix. J Biol Chem. 2004;279:28724-32 pubmed
    ..One of these, Mona/Gads, was also shown to bind HPK1 in mouse T cells in vivo...
  8. Harkiolaki M, Lewitzky M, Gilbert R, Jones E, Bourette R, Mouchiroud G, et al. Structural basis for SH3 domain-mediated high-affinity binding between Mona/Gads and SLP-76. EMBO J. 2003;22:2571-82 pubmed
    ..The Grb2-like adaptor protein Mona/Gads associates stably with the T-cell receptor signal transducer SLP-76...
  9. Ellis J, Ashman C, Burden M, Kilpatrick K, Morse M, Hamblin P. GRID: a novel Grb-2-related adapter protein that interacts with the activated T cell costimulatory receptor CD28. J Immunol. 2000;164:5805-14 pubmed
    ..We term this protein GRID for Grb2-related protein with insert domain...
  10. Bourgin C, Bourette R, Arnaud S, Liu Y, Rohrschneider L, Mouchiroud G. Induced expression and association of the Mona/Gads adapter and Gab3 scaffolding protein during monocyte/macrophage differentiation. Mol Cell Biol. 2002;22:3744-56 pubmed
    Mona/Gads is a Grb2-related, Src homology 3 (SH3) and SH2 domain-containing adapter protein whose expression is restricted to cells of hematopoietic lineage (i.e., monocytes and T lymphocytes)...
  11. Pandey P, Qin S, Ho J, Zhou J, Kreidberg J. Systems biology approach to identify transcriptome reprogramming and candidate microRNA targets during the progression of polycystic kidney disease. BMC Syst Biol. 2011;5:56 pubmed publisher
    ..miRNAs are small, regulatory non-coding RNAs, implicated in a wide spectrum of biological processes. Their expression levels are altered in several diseases including kidney cancer, diabetic nephropathy and PKD...
  12. Zhang E, Parker B, Yankee T. Gads regulates the expansion phase of CD8+ T cell-mediated immunity. J Immunol. 2011;186:4579-89 pubmed publisher
    The Gads adaptor protein is critical for TCR-mediated Ca(2+) mobilization...
  13. Shen S, Lau J, Zhu M, Zou J, Fuller D, Li Q, et al. The importance of Src homology 2 domain-containing leukocyte phosphoprotein of 76 kilodaltons sterile-alpha motif domain in thymic selection and T-cell activation. Blood. 2009;114:74-84 pubmed publisher
    ..Moreover, despite normal association between Gads and SLP-76, TCR-mediated formation of SLP-76 microclusters was impaired by the deletion of the SAM domain...
  14. Hughes C, Auger J, McGlade J, Eble J, Pearce A, Watson S. Differential roles for the adapters Gads and LAT in platelet activation by GPVI and CLEC-2. J Thromb Haemost. 2008;6:2152-9 pubmed publisher
    ..SLP-76 is constitutively associated with the adapter Gads in platelets, which also binds to tyrosine phosphorylated LAT, thereby providing a potential pathway of regulation ..
  15. Zeng L, Dalheimer S, Yankee T. Gads-/- mice reveal functionally distinct subsets of TCRbeta+ CD4-CD8- double-negative thymocytes. J Immunol. 2007;179:1013-21 pubmed
    ..The signaling pathways that regulate survival, proliferation, and differentiation remain unclear. We used Gads-deficient mice to investigate the signaling pathways that regulate these cell fates...
  16. Yamasaki S, Ishikawa E, Sakuma M, Kanagawa O, Cheng A, Malissen B, et al. LAT and NTAL mediate immunoglobulin E-induced sustained extracellular signal-regulated kinase activation critical for mast cell survival. Mol Cell Biol. 2007;27:4406-15 pubmed
    ..The IgE-induced survival of BMMCs lacking Gads, an adaptor critical for the formation of the LAT-SLP-76-phospholipase Cgamma (PLCgamma) complex, was observed to ..
  17. Dimasi N. Crystal structure of the C-terminal SH3 domain of the adaptor protein GADS in complex with SLP-76 motif peptide reveals a unique SH3-SH3 interaction. Int J Biochem Cell Biol. 2007;39:109-23 pubmed
    The Grb2-like adaptor protein GADS is essential for tyrosine kinase-dependent signaling in T lymphocytes...
  18. Hur E, Son M, Lee O, Choi Y, Park C, Lee H, et al. LIME, a novel transmembrane adaptor protein, associates with p56lck and mediates T cell activation. J Exp Med. 2003;198:1463-73 pubmed
    ..T cells expressing CD8-LIME chimera reveal that the protein associates with phosphatidylinositol 3-kinase, Grb2, Gads, and SHP2, and activates ERK1/2 and JNK but not p38...
  19. Kikuchi K, Kawasaki Y, Ishii N, Sasaki Y, Asao H, Takeshita T, et al. Suppression of thymic development by the dominant-negative form of Gads. Int Immunol. 2001;13:777-83 pubmed
    ..Here, we generated transgenic mice expressing Grf40-dSH2, an SH2-deleted dominant-negative form of Gads, which is driven by the lck proximal promoter...
  20. Liu S, Smith C, Arnold R, Kiefer F, McGlade C. The adaptor protein Gads (Grb2-related adaptor downstream of Shc) is implicated in coupling hemopoietic progenitor kinase-1 to the activated TCR. J Immunol. 2000;165:1417-26 pubmed
    The hemopoietic-specific Gads (Grb2-related adaptor downstream of Shc) adaptor protein possesses amino- and carboxyl-terminal Src homology 3 (SH3) domains flanking a central SH2 domain and a unique region rich in glutamine and proline ..
  21. Yankee T, Yun T, Draves K, Ganesh K, Bevan M, Murali Krishna K, et al. The Gads (GrpL) adaptor protein regulates T cell homeostasis. J Immunol. 2004;173:1711-20 pubmed
    Little is known about the role of the Gads (GrpL) adaptor protein in mature T cell populations. In this study we show that the effects of Gads deficiency on murine CD4(+) and CD8(+) T cells are markedly different...
  22. Yamasaki S, Takase Utsugi M, Ishikawa E, Sakuma M, Nishida K, Saito T, et al. Selective impairment of FcepsilonRI-mediated allergic reaction in Gads-deficient mice. Int Immunol. 2008;20:1289-97 pubmed publisher
    b>Gads is a Grb2-like adaptor protein expressed in hematopoietic cells. We demonstrated that mast cells from Gads(-/-) mice have selective functional defects...
  23. Harkiolaki M, Tsirka T, Lewitzky M, Simister P, Joshi D, Bird L, et al. Distinct binding modes of two epitopes in Gab2 that interact with the SH3C domain of Grb2. Structure. 2009;17:809-22 pubmed publisher
    ..A similar interaction mode is also present in a new complex of Mona/GadsSH3C with an RxxxxK epitope from the putative phosphatase HD-PTP...
  24. Fuller D, Zhu M, Koonpaew S, Nelson M, Zhang W. The importance of the Erk pathway in the development of linker for activation of T cells-mediated autoimmunity. J Immunol. 2012;189:4005-13 pubmed publisher
    ..The deletion of the critical signaling proteins Gads and RasGRP1 caused a further block in thymocyte development, but, over time, could not prevent CD4(+) T cell ..
  25. Berry D, Nash P, Liu S, Pawson T, McGlade C. A high-affinity Arg-X-X-Lys SH3 binding motif confers specificity for the interaction between Gads and SLP-76 in T cell signaling. Curr Biol. 2002;12:1336-41 pubmed
    ..b>Gads, a member of the Grb2 family of SH2 and SH3 domain-containing adaptors, mediates the formation of a complex between ..