Cited by 31Cell Adhesion Molecules ResearchT-cell and B-cell ImmunologyProtein Kinase Regulation and GTPase Signaling

Filamin A Phosphorylation at Serine 2152 by the Serine/Threonine Kinase Ndr2 Controls TCR-Induced LFA-1 Activation in T Cells

Open access
Waldt, Natalie, Seifert, Anke, Demiray, Yunus Emre, Devroe, Eric, Turk, Benjamin E., Reichardt, Peter, Mix, Charlie, Reinhold, Annegret +5 more·2018·Frontiers in Immunology

Abstract

The integrin LFA-1 (CD11a/CD18) plays a critical role in the interaction of T cells with antigen presenting cells (APCs) to promote lymphocyte differentiation and proliferation. This integrin can be present either in a closed or in an open active conformation and its activation upon T-cell receptor (TCR) stimulation is a critical step to allow interaction with APCs. In this study we demonstrate that the serine/threonine kinase Ndr2 is critically involved in the initiation of TCR-mediated LFA-1 activation (open conformation) in T cells. Ndr2 itself becomes activated upon TCR stimulation and phosphorylates the intracellular integrin binding partner Filamin A (FLNa) at serine 2152. This phosphorylation promotes the dissociation of FLNa from LFA-1, allowing for a subsequent association of Talin and Kindlin-3 which both stabilize the open conformation of LFA-1. Our data suggest that Ndr2 activation is a crucial step to initiate TCR-mediated LFA-1 activation in T cells.

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Integrity signals

Registry

Crossref · 10.3389/fimmu.2018.02852

Cites

1 of 1 references verified0 citation errors · 0 not checkable

Statistics

Claims the paper makes

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

Self-check

Percentages, sums and reported differences re-computed from the paper’s own numbers.

The self-check needs the paper’s full text.

Cites

Flagged first, then by citations

Research works printed but not linked: 72

  1. [1]Hogg N Patzak I Willenbrock F. The insider's guide to leukocyte integrin signalling and function. Nat Rev Immunol. (2011) 11: 416– 26. 10.1038/nri2986 21597477 · DOI
  2. [2]Kinashi T. Intracellular signalling controlling integrin activation in lymphocytes. Nat Rev Immunol. (2005) 5: 546– 59. 10.1038/nri1646 15965491 · DOI
  3. [3]Stewart MP McDowall A Hogg N. LFA-1-mediated adhesion is regulated by cytoskeletal restraint and by a Ca2+-dependent protease, calpain. J Cell Biol. (1998) 140: 699– 707. 10.1083/jcb.140.3.699 9456328 PMC2140165 · DOI
  4. [4]Abram CL Lowell CA. Leukocyte adhesion deficiency syndrome: a controversy solved. Immunol Cell Biol. (2009) 87: 440– 2. 10.1038/icb.2009.32 19417769 PMC4464832 · DOI
  5. [5]Takala H Nurminen E Nurmi SM Aatonen M Strandin T Takatalo M. β2 integrin phosphorylation on Thr758 acts as a molecular switch to regulate 14-3-3 and filamin binding. Blood (2008) 112: 1853– 62. 10.1182/blood-2007-12-127795 18550856 · DOI
  6. [6]Ishihara S Nishikimi A Umemoto E Miyasaka M Saegusa M Katagiri K. Dual functions of Rap1 are crucial for T-cell homeostasis and prevention of spontaneous colitis. Nat Commun. (2015) 6: 8982. 10.1038/ncomms9982 26634692 PMC4686857 · DOI
  7. [7]Li YF Tang RH Puan KJ Law SK Tan SM. The cytosolic protein talin induces an intermediate affinity integrin alphaLbeta2. J Biol Chem. (2007) 282: 24310– 9. 10.1074/jbc.M701860200 17591777 · DOI
  8. [8]Simonson WT Franco SJ Huttenlocher A. Talin1 regulates TCR-mediated LFA-1 function. J Immunol. (2006) 177: 7707– 14. 10.4049/jimmunol.177.11.7707 17114441 · DOI
  9. [9]Wernimont SA Wiemer AJ Bennin DA Monkley SJ Ludwig T Critchley DR. Contact-dependent T cell activation and T cell stopping require talin1. J Immunol. (2011) 187: 6256– 67. 10.4049/jimmunol.1102028 22075696 PMC3237745 · DOI
  10. [10]Kondo N Ueda Y Kita T Ozawa M Tomiyama T Yasuda K. NDR1-dependent regulation of kindlin-3 controls high-affinity LFA-1 binding and immune synapse organization. Mol Cell Biol. (2017) 37: e00424– 16. 10.1128/MCB.00424-16 28137909 PMC5376635 · DOI
  11. [11]Manevich-Mendelson E Feigelson SW Pasvolsky R Aker M Grabovsky V Shulman Z Kilic Loss of Kindlin-3 in LAD-III eliminates LFA-1 but not VLA-4 adhesiveness developed under shear flow conditions. Blood (2009) 114: 2344– 53. 10.1182/blood-2009-04-218636 19617577 · DOI
  12. [12]Margadant C Monsuur HN Norman JC Sonnenberg A Mechanisms of integrin activation and trafficking Curr Opin Cell Biol. (2011) 23: 607– 14. 10.1016/j.ceb.2011.08.005 21924601 · DOI
  13. [13]Gahmberg CG Fagerholm SC Nurmi SM Chavakis T Marchesan S Gronholm M. Regulation of integrin activity and signalling. Biochim Biophys Acta (2009) 1790: 431– 44. 10.1016/j.bbagen.2009.03.007 19289150 PMC2734279 · DOI
  14. [14]Kiema T Lad Y Jiang P Oxley CL Baldassarre M Wegener KL. The molecular basis of filamin binding to integrins and competition with talin. Mol Cell (2006) 21: 337– 47. 10.1016/j.molcel.2006.01.011 16455489 · DOI · Paper page
  15. [15]Bos JL de Rooij J Reedquist KA Rap1 signaling: adhering to new models. Nat Rev Mol Cell Biol. (2001) 2: 369– 77. 10.1038/35073073 11331911 · DOI
  16. [16]Katagiri K Maeda A Shimonaka M Kinashi T. RAPL, a Rap1-binding molecule that mediates Rap1-induced adhesion through spatial regulation of LFA-1. Nat Immunol. (2003) 4: 741– 8. 10.1038/ni950 12845325 · DOI
  17. [17]Lafuente EM van Puijenbroek AA Krause M Carman CV Freeman GJ Berezovskaya A. RIAM, an Ena/VASP and profilin ligand, interacts with Rap1-GTP and mediates Rap1-induced adhesion. Dev Cell (2004) 7: 585– 95. 10.1016/j.devcel.2004.07.021 15469846 · DOI
  18. [18]Patsoukis N Bardhan K Weaver JD Sari D Torres-Gomez A Li L. The adaptor molecule RIAM integrates signaling events critical for integrin-mediated control of immune function and cancer progression. Sci Signal (2017) 10: eaam8298. 10.1126/scisignal.aam8298 28831022 · DOI
  19. [19]Witte A Degen J Baumgart K Waldt N Kuropka B Freund C Emerging roles of ADAP, SKAP55, and SKAP-HOM for integrin and NF-κB signaling in T cells. Clin Cell Immunol. (2012) S 12: 002 1– 8. 10.4172/2155-9899.S12-002 · DOI
  20. [20]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. 10.1016/j.tcb.2008.07.005 18760924 PMC3512129 · DOI
  21. [21]Griffiths EK Krawczyk C Kong YY Raab M Hyduk SJ Bouchard D. Positive regulation of T cell activation and integrin adhesion by the adapter Fyb/Slap. Science (2001) 293: 2260– 3. 10.1126/science.1063397 11567140 · DOI
  22. [22]Peterson EJ Woods ML Dmowski SA Derimanov G Jordan MS Wu JN. Coupling of the TCR to integrin activation by Slap-130/Fyb. Science (2001) 293: 2263– 5. 10.1126/science.1063486 11567141 · DOI
  23. [23]Wang H Moon EY Azouz A Wu X Smith A Schneider H. SKAP-55 regulates integrin adhesion and formation of T cell-APC conjugates. Nat Immunol. (2003) 4: 366– 74. 10.1038/ni913 12652296 · DOI
  24. [24]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. 10.1128/MCB.02011-06 17403904 PMC1900018 · DOI
  25. [25]Raab M Wang H Lu Y Smith X Wu Z Strebhardt K. 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. 10.1016/j.immuni.2010.03.007 20346707 PMC3812847 · DOI
  26. [26]Lim D Lu Y Rudd CE. Non-cleavable talin rescues defect in the T-cell conjugation of T-cells deficient in the immune adaptor SKAP1. Immunol Lett. (2016) 172: 40– 46. 10.1016/j.imlet.2016.02.004 26905930 PMC4860717 · DOI
  27. [27]Ophir MJ Liu BC Bunnell SC. The N terminus of SKAP55 enables T cell adhesion to TCR and integrin ligands via distinct mechanisms. J Cell Biol. (2013) 203: 1021– 41. 10.1083/jcb.201305088 24368808 PMC3871428 · DOI
  28. [28]Raab M Smith X Matthess Y Strebhardt K Rudd CE. SKAP1 protein PH domain determines RapL membrane localization and Rap1 protein complex formation for T cell receptor (TCR) activation of LFA-1. J Biol Chem. (2011) 286: 29663– 70. 10.1074/jbc.M111.222661 21669874 PMC3191007 · DOI
  29. [29]Raab M Lu Y Kohler K Smith X Strebhardt K Rudd CE. LFA-1 activates focal adhesion kinases FAK1/PYK2 to generate LAT-GRB2-SKAP1 complexes that terminate T-cell conjugate formation. Nat Commun. (2017) 8: 16001. 10.1038/ncomms16001 28699640 PMC5510181 · DOI
  30. [30]Avruch J Zhou D Fitamant J Bardeesy N Mou F Barrufet LR. Protein kinases of the Hippo pathway: regulation and substrates. Semin Cell Dev Biol. (2012) 23: 770– 84. 10.1016/j.semcdb.2012.07.002 22898666 PMC3489012 · DOI
  31. [31]Katagiri K Imamura M Kinashi T. Spatiotemporal regulation of the kinase Mst1 by binding protein RAPL is critical for lymphocyte polarity and adhesion. Nat Immunol. (2006) 7: 919– 28. 10.1038/ni1374 16892067 · DOI
  32. [32]Katagiri K Katakai T Ebisuno Y Ueda Y Okada T Kinashi T. Mst1 controls lymphocyte trafficking and interstitial motility within lymph nodes. EMBO J. (2009) 28: 1319– 31. 10.1038/emboj.2009.82 19339990 PMC2683056 · DOI
  33. [33]Zhou D Medoff BD Chen L Li L Zhang XF Praskova M. The Nore1B/Mst1 complex restrains antigen receptor-induced proliferation of naive T cells. Proc Natl Acad Sci USA (2008) 105: 20321– 6. 10.1073/pnas.0810773105 19073936 PMC2600581 · DOI
  34. [34]Hergovich A Stegert MR Schmitz D Hemmings BA. NDR kinases regulate essential cell processes from yeast to humans. Nat Rev Mol Cell Biol. (2006) 7: 253– 64. 10.1038/nrm1891 16607288 · DOI
  35. [35]Hergovich A. The roles of NDR protein kinases in hippo signalling. Genes (2016) 7: 1– 16. 10.3390/genes7050021 27213455 PMC4880841 · DOI
  36. [36]Tang F Gill J Ficht X Barthlott T Cornils H Schmitz-Rohmer D. The kinases NDR1/2 act downstream of the Hippo homolog MST1 to mediate both egress of thymocytes from the thymus and lymphocyte motility. Sci Signal (2015) 8: ra100. 10.1126/scisignal.aab2425 26443704 · DOI
  37. [37]Schmitz-Rohmer D Probst S Yang ZZ Laurent F Stadler MB Zuniga A. NDR kinases are essential for somitogenesis and cardiac looping during mouse embryonic development. PLoS ONE (2015) 10: e0136566. 10.1371/journal.pone.0136566 26305214 PMC4549247 · DOI
  38. [38]Cornils H Stegert MR Hergovich A Hynx D Schmitz D Dirnhofer S. Ablation of the kinase NDR1 predisposes mice to the development of T cell lymphoma. Sci Signal (2010) 3: ra47. 10.1126/scisignal.2000681 20551432 · DOI · Paper page
  39. [39]Demiray YE Rehberg K Kliche S Stork O. Ndr2 kinase controls neurite outgrowth and dendritic branching through α1 integrin expression. Front Mol Neurosci. (2018) 11: 66. 10.3389/fnmol.2018.00066 29559888 PMC5845635 · DOI · Paper page
  40. [40]Rehberg K Kliche S Madencioglu DA Thiere M Müller B Meineke BM. The serine/threonine kinase Ndr2 controls integrin trafficking and integrin-dependent neurite growth. J Neurosci. (2014) 34: 5342– 54. 10.1523/JNEUROSCI.2728-13.2014 24719112 PMC6609001 · DOI · Paper page
  41. [41]Kliche S Breitling D Togni M Pusch R Heuer K Wang X. 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. 10.1128/MCB.00331-06 16980616 PMC1592884 · DOI
  42. [42]Devroe E Erdjument-Bromage H Tempst P Silver PA. Human Mob proteins regulate the NDR1 and NDR2 serine-threonine kinases. J Biol Chem. (2004) 279: 24444– 5 10.1074/jbc.M401999200 15067004 · DOI
  43. [43]Muriel O Echarri A Hellriegel C Pavón DM Beccari L Del Pozo MA. Phosphorylated filamin A regulates actin-linked caveolae dynamics. J Cell Sci. (2011) 124: 2763– 76. 10.1242/jcs.080804 21807941 · DOI
  44. [44]Travis MA van der Flier A Kammerer RA Mould AP Sonnenberg A Humphries MJ. Interaction of filamin A with the integrin beta 7 cytoplasmic domain: role of alternative splicing and phosphorylation. FEBS Lett. (2004) 569: 185– 90. 10.1016/j.febslet.2004.04.099 15225631 · DOI
  45. [45]Moser M Bauer M Schmid S Ruppert R Schmidt S Sixt M. Kindlin-3 is required for beta2 integrin-mediated leukocyte adhesion to endothelial cells. Nat Med. (2009) 15: 300– 5. 10.1038/nm.1921 19234461 · DOI
  46. [47]Witte A Meineke B Sticht J Philipsen L Kuropka B Müller AJ. D120 and K152 within the PH Domain of T cell adapter SKAP55 regulate plasma membrane targeting of SKAP55 and LFA-1 affinity modulation in human T lymphocytes. Mol Cell Biol. (2017) 37: e00509– 16. 10.1128/MCB.00509-16 28052935 PMC5359422 · DOI
  47. [48]Parzmair GP Gereke M Haberkorn O Annemann M Podlasly L Kliche S. 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. 10.1189/jlb.1A0216-090RR 27605210 · DOI
  48. [49]Horn J Wang X Reichardt P Stradal TE Warnecke N Simeoni L. 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. 10.4049/jimmunol.0900649 19812192 · DOI
  49. [50]Wang X Simeoni L Lindquist JA Saez-Rodriguez J Ambach A Gilles ED. Dynamics of proximal signaling events after TCR/CD8-mediated induction of proliferation or apoptosis in mature CD8+ T cells. J Immunol. (2008) 180: 6703– 12. 10.4049/jimmunol.180.10.6703 18453590 · DOI
  50. [51]Kliche S Worbs T Wang X Degen J Patzak I Meineke B. CCR7-mediated LFA-1 functions in T cells are regulated by 2 independent ADAP/SKAP55 modules. Blood (2012) 119: 777– 85. 10.1182/blood-2011-06-362269 22117043 · DOI
  51. [52]Hutti JE Jarrell ET Chang JD Abbott DW Storz P Toker A. A rapid method for determining protein kinase phosphorylation specificity. Nat Methods (2004) 1: 27– 9. 10.1038/nmeth708 15782149 · DOI
  52. [53]Sato T Ishii J Ota Y Sasaki E Shibagaki Y Hattori S. Mammalian target of rapamycin (mTOR) complex 2 regulates filamin A-dependent focal adhesion dynamics and cell migration. Genes Cells (2016) 21: 579– 93. 10.1111/gtc.12366 27059097 · DOI
  53. [54]Suzuki JI Yamasaki S Wu J Koretzky GA Saito T. The actin cloud induced by LFA-1–mediated outside-in signals lowers the threshold for T-cell activation. Blood (2007) 109: 168– 75. 10.1182/blood-2005-12-020164 16973965 · DOI
  54. [55]Perez OD Mitchell D Jager GC South S Murriel C McBride J. Leukocyte functional antigen 1 lowers T cell activation thresholds and signaling through cytohesin-1 and Jun-activating binding protein 1. Nat Immunol. (2003) 4: 1083– 92. 10.1038/ni984 14528303 · DOI
  55. [56]Stegert MR Hergovich A Tamaskovic R Bichsel SJ Hemmings B. Regulation of NDR protein kinase by hydrophobic motif phosphorylation mediated by the mammalian Ste20-like kinase MST3. Mol Cell Biol. (2005). 25: 11019– 29. 10.1128/MCB.25.24.11019-11029.2005 16314523 PMC1316964 · DOI · Paper page
  56. [57]Ravid D Chuderland D Landsman L Lavie Y Reich R Liscovitch M. Filamin A is a novel caveolin-1-dependent target in IGF-I-stimulated cancer cell migration. Exp Cell Res. (2008) 314: 2762– 73. 10.1016/j.yexcr.2008.06.004 18598695 · DOI
  57. [58]Woo MS Ohta Y Rabinovitz I Stossel TP Blenis J. Ribosomal S6 kinase (RSK) regulates phosphorylation of filamin A on an important regulatory site. Mol Cell Biol. (2004) 24: 3025– 35. 10.1128/MCB.24.7.3025-3035.2004 15024089 PMC371131 · DOI
  58. [59]Li L Lu L Chen F Filamin A phosphorylation by Akt promotes cell migration in response to arsenic. Oncotarget (2015) 20: 12009– 19. 10.18632/oncotarget.3617 PMC4494919 25944616 · DOI
  59. [60]Davies P Shizuta Y Olden K Gallo M Pastan I. Phosphorylation of filamin and other proteins in cultured fibroblasts. Biochem Biophys Res Commun. (1977) 74: 300– 7. 10.1016/0006-291X(77)91408-5 189763 · DOI
  60. [61]Wallach D Davies PJ Pastan I. Cyclic AMP-dependent phosphorylation of filamin in mammalian smooth muscle. J Biol Chem. (1978) 253: 4739– 45. 207708
  61. [62]Carroll RC Gerrard JM. Phosphorylation of platelet actin-binding protein during platelet activation. Blood (1982) 59: 466– 71. 7199358
  62. [63]Chen M Stracher A. In situ phosphorylation of platelet actin-binding protein by cAMP-dependent protein kinase stabilizes it against proteolysis by calpain. J Biol Chem (1989) 264: 14282– 9. 2547793
  63. [64]Wu MP Jay D Stracher A. Existence of multiple phosphorylated forms of human platelet actin binding protein. Cell Mol Biol Res. (1994) 40: 351– 7. 7866435
  64. [65]Pons M Izquierdo I Andreu-Carbo M Garrido G Planagumà J Muriel O. Phosphorylation of filamin A regulates chemokine receptor CCR2 recycling. J Cell Sci (2017) 130: 490– 501. 10.1242/jcs.193821 27909248 · DOI
  65. [66]Feigelson SW Grabovsky V Manevich-Mendelson E Pasvolsky R Shulman Z. Kindlin-3 is required for the stabilization of TCR-stimulated LFA-1:ICAM-1 bonds critical for lymphocyte arrest and spreading on dendritic cells. Blood (2011) 117: 7042– 52. 10.1182/blood-2010-12-322859 21536861 · DOI
  66. [67]Morrison VL Uotila LM Llort Asens M Savinko T Fagerholm SC. Optimal T cell activation and B cell antibody responses in vivo require the interaction between leukocyte function-associated antigen-1 and kindlin-3. J Immunol. (2015) 195: 105– 15. 10.4049/jimmunol.1402741 25987740 · DOI
  67. [68]Vadlamudi RK Li F Adam L Nguyen D Ohta Y Stossel TP. Filamin is essential in actin cytoskeletal assembly mediated by p21-activated kinase 1. Nat Cell Biol. (2002) 4: 681– 90. 10.1038/ncb838 12198493 · DOI
  68. [69]Phee H Abraham RT Weiss A. Dynamic recruitment of PAK1 to the immunological synapse is mediated by PIX independently of SLP-76 and Vav1. Nat Immunol. (2005) 6: 608– 17. 10.1038/ni1199 15864311 · DOI
  69. [70]Missy K Hu B Schilling K Harenberg A Sakk V Kuchenbecker K. AlphaPIX Rho GTPase guanine nucleotide exchange factor regulates lymphocyte functions and antigen receptor signaling. Mol Cell Biol. (2008) 28: 3776– 89. 10.1128/MCB.00507-07 18378701 PMC2423308 · DOI
  70. [71]Ku GM Yablonski D Manser E Lim L Weiss A. A PAK1-PIX-PKL complex is activated by the T-cell receptor independent of Nck, Slp-76 and LAT. EMBO J. (2001) 20: 457– 65. 10.1093/emboj/20.3.457 11157752 PMC133476 · DOI
  71. [72]Kim MJ Kim E Ryu SH Suh PG. The mechanism of phospholipase C-gamma1 regulation. Exp Mol Med. (2000) 32: 101– 9. 10.1038/emm.2000.18 11048639 · DOI
  72. [73]Katagiri K Shimonaka M Kinashi T. Rap1-mediated lymphocyte function-associated antigen-1 activation by the T cell antigen receptor is dependent on phospholipase C-gamma1. J Biol Chem. (2004) 279: 11875– 81. 10.1074/jbc.M310717200 14702343 · DOI

Cited by

Sorted by citations

Authors
Waldt, N., Seifert, A., Demiray, Y. E., Devroe, E., Turk, B. E., Reichardt, P., Mix, C., Reinhold, A., Freund, C., Müller, A. J., Schraven, B., Stork, O., & Kliche, S.
Affiliations
  • Otto-von-Guericke-Universität Magdeburg (DE)
  • The University of Texas MD Anderson Cancer Center (US)
  • Yale University (US)
  • Freie Universität Berlin (DE)
  • Helmholtz Centre for Infection Research (DE)
  • Center for Behavioral Brain Sciences (DE)
Corresponding author
  • Schraven, Burkhart
  • Stork, Oliver
  • Kliche, Stefanie
Venue
Frontiers in Immunology
Published
2018-12-04
Volume
9
Pages
2852-2852
ISSN
1664-3224 (ISSN-L)
OpenAlex
W2902466408
Cited by
31
References
1
Citations by year
2026: 4 · 2025: 7 · 2024: 3 · 2023: 2 · 2022: 2 · 2021: 5 · 2020: 6 · 2019: 2
FWCI
2.88
Type
journal article
Language
en
Open access
Locations
  • Frontiers in Immunology (publishedVersion, cc-by)
  • Europe PMC (PubMed Central) (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
  • HZI (Helmholtz Centre for Infection Research) (submittedVersion, cc-by-nc-sa)
  • Refubium (Universitätsbibliothek der Freien Universität Berlin) (submittedVersion, cc-by)
  • Universitätsbibliothek der FU Berlin Hochschulschriftenstelle u. Dokumentenserver (cc-by)
Funders
Deutsche Forschungsgemeinschaft (CRC854/B10, and Z01, CRC854)
Topics
  • Health Sciences › Medicine › Immunology and Allergy › Cell Adhesion Molecules Research
  • Life Sciences › Immunology and Microbiology › Immunology › T-cell and B-cell Immunology
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Kinase Regulation and GTPase Signaling
Keywords
filamin A, LFA-1, integrin activation, T cell receptor signaling, serine phosphorylation, talin, kindlin-3, integrin conformation, T cell-APC interaction
MeSH terms
Animals, Cells, Cultured, Cytoskeletal Proteins, Humans, Lymphocyte Activation, Membrane Proteins, Mutation, Neoplasm Proteins, Phosphorylation, Proteins, Receptors, Antigen, T-Cell, Serine, T-Lymphocytes, Lymphocyte Function-Associated Antigen-1, Talin, Protein Serine-Threonine Kinases, Mice, Knockout, CD18 Antigens, Jurkat Cells, Adaptor Proteins, Signal Transducing, Mice, HEK293 Cells, Primary Cell Culture, Healthy Volunteers, Filamins

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

Are you an author, or do you see a problem with this page? Request a review