Encyclopedia of Signaling Molecules

2018 Edition
| Editors: Sangdun Choi


  • Ana Kasirer-FriedeEmail author
Reference work entry
DOI: https://doi.org/10.1007/978-3-319-67199-4_577


Historical Background

The adhesion and degranulation promoting adapter protein (ADAP) is a large protein which is alternatively spliced to produce a 120 or a 130 kDa isoform and is expressed in T cells, proB cells (but not mature B cells), and myeloid cells. ADAP was first cloned in 1997 by two independent labs that were working to elucidate signaling pathways induced by engagement of the T cell receptor. In early studies, the kinase, Fyn-T, was found to be an important mediator of mature, peripheral T cell activation. In order to identify potential substrates of Fyn-T, da Silva et al. used GST–FYN-SH2 domain fusion proteins to immunoprecipitate a 120/130 kDa phosphorylated protein from a TCR/antiCD3 stimulated T cell line. An antibody developed against this protein was used to screen a Jurkat cell line cDNA library and led to the cloning of ADAP. In the same year, Musci et al. used a chimeric...

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  1. Asazuma N, Wilde JI, Berlanga O, Leduc M, Leo A, Schweighoffer E, Tybulewicz V, Bon C, Liu SK, McGlade CJ, Schraven B, Watson SP. Interaction of linker for activation of T cells with multiple adapter proteins in platelets activated by the glycoprotein VI-selective ligand, convulxin. J Biol Chem. 2000;275:33427–34.PubMedCrossRefGoogle Scholar
  2. de la Puerta ML, Trinidad AG, del Carmen RM, Bogetz J, Sanchez Crespo M, Mustelin T, et al. Characterization of new substrates targeted by Yersinia tyrosine phosphatase YopH. PLoS One. 2009;4:e4431.PubMedPubMedCentralCrossRefGoogle Scholar
  3. Engelmann S, Togni M, Kliche S, Reinhold D, Schraven B, Reinhold A. The adhesion- and degranulation-promoting adaptor protein and its role in the modulation of experimental autoimmune encephalomyelitis. Crit Rev Immunol. 2015;35:1–14.PubMedCrossRefGoogle Scholar
  4. Fiege JK, Burbach BJ, Shimizu Y. Negative regulation of memory phenotype CD8 T cell conversion by adhesion and degranulation-promoting adapter protein. J Immunol. 2015;195:3119–28.PubMedPubMedCentralCrossRefGoogle Scholar
  5. Hamamy H, Makrythanasis P, Al-Allawi N, Muhsin AA, Antonarakis SE. Recessive Thrombocytopenia likely due to a Homozygous Pathogenic Variant in the FYBgene: case report. BMC Med Genet. 2014;15:135.  https://doi.org/10.1186/s12881-014-0135-0.CrossRefPubMedPubMedCentralGoogle Scholar
  6. Heuer K, Kofler M, Langdon G, Thiemke K, Freund C. Structure of a helically extended SH3 domain of the T cell adapter protein ADAP. Stucture. 2004;12:603–10.CrossRefGoogle Scholar
  7. Horn J, Wang X, Reichardt P, Stradal TE, Warnecke N, Simeoni L, et al. Src homology 2-domain containing leukocyte-specific phosphoprotein of 76 kDa is mandatory for TCR-mediated inside-out signaling, but dispensable for CXCR4-mediated LFA-1 activation, adhesion, and migration of T cells. J Immunol. 2009;183:5756–67.PubMedCrossRefGoogle Scholar
  8. Jordan MS, Koretzky GA. Coordination of receptor signaling in multiple hematopoietic cell lineages by the adaptor protein SLP-76. Cold Spring Harb Perspect Biol. 2010;2(4):a002501.PubMedPubMedCentralCrossRefGoogle Scholar
  9. Kasirer-Friede A, Ruggeri ZM, Shattil SJ. Role for ADAP in shear flow-induced platelet mechanotransduction. Blood. 2010;115:2274–82.PubMedPubMedCentralCrossRefGoogle Scholar
  10. Kasirer-Friede A, Kang J, Kahner B, Ye F, Ginsberg MH, Shattil SJ. ADAP interactions with talin and kindlin promote platelet integrin alphaIIbbeta3 activation and stable fibrinogen binding. Blood. 2014;123:3156–65.PubMedPubMedCentralCrossRefGoogle Scholar
  11. Kliche S, Breitling D, Togni M, Pusch R, Heuer K, Wang X, et al. The ADAP/SKAP55 signaling module regulates T-cell receptor-mediated integrin activation through plasma membrane targeting of Rap1. Mol Cell Biol. 2006;26:7130–44.PubMedPubMedCentralCrossRefGoogle Scholar
  12. Koga S, Yogo K, Yoshikawa K, Samori H, Goto M, Uchida T, Ishida N, Takeya T. Physical and functional association of c-Src and adhesion and degranulation promoting adaptor protein (ADAP) in osteoclastogenesis in vitro. J Biol Chem. 2005;280:31564–71.PubMedCrossRefGoogle Scholar
  13. Kuropka B, Witte A, Sticht J, Waldt N, Majkut P, Hackenberger CP, et al. Analysis of phosphorylation-dependent protein interactions of adhesion and degranulation promoting adaptor protein (ADAP) reveals novel interaction partners required for chemokine-directed t cell migration. Mol Cell Proteomics. 2015;14:2961–72.PubMedPubMedCentralCrossRefGoogle Scholar
  14. Levin C, Koren A, Pretorius E, Rosenberg N, Shenkman B, Hauschner H, et al. Deleterious mutation in the FYB gene is associated with congenital autosomal recessive small-platelet thrombocytopenia. J Thromb Haemost. 2015;13:1285–92.PubMedCrossRefGoogle Scholar
  15. Litvinov IV, Netchiporouk E, Cordeiro B, Dore MA, Moreau L, Pehr K, et al. The use of transcriptional profiling to improve personalized diagnosis and management of cutaneous t-cell lymphoma (CTCL). Clin Cancer Res. 2015;21:2820–9.PubMedPubMedCentralCrossRefGoogle Scholar
  16. Medeiros RB, Burbach BJ, Mueller KL, Srivastava R, Moon JJ, Highfill S, Peterson EJ, Shimizu Y. Regulation of NF-κB activation in T cells via association of the adapter proteins ADAP and CARMA1. Sci. 2007;316:754–8.CrossRefGoogle Scholar
  17. Menasche G, Kliche S, Chen EJ, Stradal TE, Schraven B, Koretzky G. RIAM links the ADAP/SKAP-55 signaling module to Rap1, facilitating T-cell-receptor-mediated integrin activation. Mol Cell Biol. 2007;27:4070–81.PubMedPubMedCentralCrossRefGoogle Scholar
  18. Parzmair GP, Gereke M, Haberkorn O, Annemann M, Podlasly L, Kliche S, Reinhold A, Schraven B, Bruder D. ADAP plays a pivotal role in CD4+ T cell activation but is only marginally involved in CD8+ T cell activation, differentiation, and immunity to pathogens. J leukoc Biol. 2017;101:407–19.PubMedCrossRefGoogle Scholar
  19. Patzak IM, Konigsberger S, Suzuki A, Mak TW, Kiefer F. HPK1 competes with ADAP for SLP-76 binding and via Rap1 negatively affects T-cell adhesion. Eur J Immunol. 2010;40:3220–5.PubMedCrossRefGoogle Scholar
  20. Peterson EJ. The TCR ADAPts to integrin-mediated cell adhesion. Immunol Rev. 2003;192:113–21.PubMedCrossRefGoogle Scholar
  21. Raab M, Wang H, Lu Y, Smith X, Wu Z, Strebhardt K, et al. T cell receptor “inside-out” pathway via signaling module SKAP1-RapL regulates T cell motility and interactions in lymph nodes. Immunity. 2010;32:541–56.PubMedCrossRefGoogle Scholar
  22. Srivastava R, Burbach BJ, Shimizu Y. NF-kappaB activation in T cells requires discrete control of IkappaB kinase alpha/beta (IKKalpha/beta) phosphorylation and IKKgamma ubiquitination by the ADAP adapter protein. J Biol Chem. 2010;285:11100–5.PubMedPubMedCentralCrossRefGoogle Scholar
  23. Sylvester M, Kliche S, Lange S, Geithner S, Klemm C, Schlosser A, et al. Adhesion and degranulation promoting adapter protein (ADAP) is a central hub for phosphotyrosine-mediated interactions in T cells. PLoS One. 2010;5:e11708.PubMedPubMedCentralCrossRefGoogle Scholar
  24. Wang H, Rudd CE. SKAP-55, SKAP-55-related and ADAP adaptors modulate integrin-mediated immune-cell adhesion. Trends Cell Biol. 2008;18:486–93.PubMedPubMedCentralCrossRefGoogle Scholar
  25. Witte A, Degen J, Baumgart K, Waldt N, Kuropka B, Freund C, et al. Emerging roles of ADAP, SKAP55, and SKAP-HOM for integrin and NF-kB signaling in T cells. J Clin Cell Immunol 2012; S12.  https://doi.org/10.4172/2155-9899.S12-002
  26. Zimmermann J, Kuhne R, Sylvester M, Freund C. Redox-regulated conformational changes in an SH3 domain. Biochemistry. 2007;46:6971–7.PubMedCrossRefGoogle Scholar

Copyright information

© Springer International Publishing AG 2018

Authors and Affiliations

  1. 1.Department of MedicineUniversity of California, San DiegoLa JollaUSA