O. Acuto, D. Bartolo, V. Michel, and F. , Tailoring T-cell receptor signals by proximal negative feedback mechanisms, Nature Reviews Immunology, vol.19, issue.9, pp.699-712, 2008.
DOI : 10.1038/nri2397

URL : https://hal.archives-ouvertes.fr/pasteur-00369557

H. Ai, J. Henderson, S. Remington, and R. Campbell, cyan fluorescent protein: structural characterization and applications in fluorescence imaging, Biochemical Journal, vol.400, issue.3, pp.531-540, 2006.
DOI : 10.1042/BJ20060874

E. Astoul, C. Edmunds, D. Cantrell, and S. Ward, PI 3-K and T-cell activation: limitations of T-leukemic cell lines as signaling models, Trends in Immunology, vol.22, issue.9, pp.490-496, 2001.
DOI : 10.1016/S1471-4906(01)01973-1

K. Bachmaier, C. Krawczyk, I. Kozieradzki, Y. Kong, T. Sasaki et al., Negative regulation of lymphocyte activation and autoimmunity by the molecular adaptor Cbl-b, Nature, vol.403, pp.211-216, 2000.

L. Balagopalan, B. Ashwell, K. Bernot, I. Akpan, N. Quasba et al., Enhanced T-cell signaling in cells bearing linker for activation of T-cell (LAT) molecules resistant to ubiquitylation, Proceedings of the National Academy of Sciences, vol.108, issue.7, pp.2885-2890, 2011.
DOI : 10.1073/pnas.1007098108

M. Bamberger, A. Santos, C. Goncalves, M. Oliveira, J. James et al., A New Pathway of CD5 Glycoprotein-mediated T Cell Inhibition Dependent on Inhibitory Phosphorylation of Fyn Kinase, Journal of Biological Chemistry, vol.286, issue.35, pp.30324-30336, 2011.
DOI : 10.1074/jbc.M111.230102

G. Bindea, B. Mlecnik, H. Hackl, P. Charoentong, M. Tosolini et al., ClueGO: a Cytoscape plug-in to decipher functionally grouped gene ontology and pathway annotation networks, Bioinformatics, vol.25, issue.8, pp.1091-1093, 2009.
DOI : 10.1093/bioinformatics/btp101

T. Brdicka, D. Pavlistova, A. Leo, E. Bruyns, V. Korinek et al., Phosphoprotein Associated with Glycosphingolipid-Enriched Microdomains (Pag), a Novel Ubiquitously Expressed Transmembrane Adaptor Protein, Binds the Protein Tyrosine Kinase Csk and Is Involved in Regulation of T Cell Activation, The Journal of Experimental Medicine, vol.11, issue.9, pp.1591-1604, 2000.
DOI : 10.1021/ac00096a002

C. Brossard, M. Semichon, A. Trautmann, and G. Bismuth, CD5 Inhibits Signaling at the Immunological Synapse Without Impairing Its Formation, The Journal of Immunology, vol.170, issue.9, 2003.
DOI : 10.4049/jimmunol.170.9.4623

L. Buday, A. Khwaja, S. Sipeki, A. Farago, and J. Downward, Interactions of Cbl with two adapter proteins, Grb2 and Crk, upon T cell activation, J Biol Chem, vol.271, pp.6159-6163, 1996.

A. Catic, Z. Sun, D. Ratner, S. Misaghi, E. Spooner et al., Sequence and structure evolved separately in a ribosomal ubiquitin variant, The EMBO Journal, vol.20, issue.14, pp.3474-3483, 2007.
DOI : 10.1038/sj.emboj.7601772

A. Chakraborty and A. Weiss, Insights into the initiation of TCR signaling, Nature Immunology, vol.12, issue.9, pp.798-807, 2014.
DOI : 10.1016/0092-8674(93)90511-N

Y. Chiang, H. Kole, K. Brown, M. Naramura, S. Fukuhara et al., Cbl-b regulates the CD28 dependence of T-cell activation, Nature, vol.403, pp.216-220, 2000.

J. Chiang, I. Jang, R. Hodes, and H. Gu, Ablation of Cbl-b provides protection against transplanted and spontaneous tumors, Journal of Clinical Investigation, vol.117, issue.4, pp.1029-1036, 2007.
DOI : 10.1172/JCI29472

B. Collins, L. Gillet, G. Rosenberger, H. Rost, A. Vichalkovski et al., Quantifying protein interaction dynamics by SWATH mass spectrometry: application to the 14-3-3 system, Nature Methods, vol.11, issue.12, pp.1246-1253, 2013.
DOI : 10.1093/database/baq023

P. Croise, C. Estay-ahumada, S. Gasman, and S. Ory, Rho GTPases, phosphoinositides, and actin, Small GTPases, vol.112, issue.2, p.29469, 2014.
DOI : 10.1016/j.devcel.2010.11.006

D. Davidson, M. Bakinowski, M. Thomas, V. Horejsi, and A. Veillette, Phosphorylation-Dependent Regulation of T-Cell Activation by PAG/Cbp, a Lipid Raft-Associated Transmembrane Adaptor, Molecular and Cellular Biology, vol.23, issue.6, pp.2017-2028, 2003.
DOI : 10.1128/MCB.23.6.2017-2028.2003

G. Davies, S. Ettenberg, A. Coats, M. Mussante, S. Ravichandran et al., Cbl-b interacts with ubiquitinated proteins; differential functions of the UBA domains of c-Cbl and Cbl-b, Oncogene, vol.23, issue.42, pp.7104-7115, 2004.
DOI : 10.1038/sj.onc.1207952

D. Demydenko, c-Cbl mediated ubiquitylation and regulation of cell surface exposure of CD5, Biochemical and Biophysical Research Communications, vol.392, issue.4, pp.500-504, 2010.
DOI : 10.1016/j.bbrc.2010.01.052

K. Dennehy, R. Broszeit, W. Ferris, and A. Beyers, Thymocyte activation induces the association of the proto-oncoprotein c-cbl and ras GTPase- activating protein with CD5, European Journal of Immunology, vol.116, issue.5, pp.1617-1625, 1998.
DOI : 10.1002/(SICI)1521-4141(199805)28:05<1617::AID-IMMU1617>3.0.CO;2-7

M. Dobenecker, C. Schmedt, M. Okada, and A. Tarakhovsky, The Ubiquitously Expressed Csk Adaptor Protein Cbp Is Dispensable for Embryogenesis and T-Cell Development and Function, Molecular and Cellular Biology, vol.25, issue.23, pp.10533-10542, 2005.
DOI : 10.1128/MCB.25.23.10533-10542.2005

D. Fang and Y. Liu, Proteolysis-independent regulation of PI3K by Cbl-bmediated ubiquitination in T cells, Nature Immunology, vol.275, issue.9, pp.870-875, 2001.
DOI : 10.1038/ni0901-870

E. Feshchenko, E. Smirnova, G. Swaminathan, A. Teckchandani, R. Agrawal et al., TULA: an SH3- and UBA-containing protein that binds to c-Cbl and ubiquitin, Oncogene, vol.23, issue.27, pp.4690-4706, 2004.
DOI : 10.1038/sj.onc.1207627

S. Gelkop, Y. Babichev, and N. Isakov, T Cell Activation Induces Direct Binding of the Crk Adapter Protein to the Regulatory Subunit of Phosphatidylinositol 3-Kinase (p85) via a Complex Mechanism Involving the Cbl Protein, Journal of Biological Chemistry, vol.276, issue.39, pp.36174-36182, 2001.
DOI : 10.1074/jbc.M100731200

A. Gingras, M. Gstaiger, B. Raught, and R. Aebersold, Analysis of protein complexes using mass spectrometry, Nature Reviews Molecular Cell Biology, vol.42, issue.8, pp.645-654, 2007.
DOI : 10.1038/nrm2208

J. Gorman, A. Babich, C. Dick, R. Schoon, A. Koenig et al., The Cytoskeletal Adaptor Protein IQGAP1 Regulates TCR-Mediated Signaling and Filamentous Actin Dynamics, The Journal of Immunology, vol.188, issue.12, pp.6135-6144, 2012.
DOI : 10.4049/jimmunol.1103487

M. Gronski, J. Boulter, D. Moskophidis, L. Nguyen, K. Holmberg et al., TCR affinity and negative regulation limit autoimmunity, Nature Medicine, vol.150, issue.11, pp.1234-1239, 2004.
DOI : 10.1084/jem.20010032

K. Haglund and I. Dikic, The role of ubiquitylation in receptor endocytosis and endosomal sorting, Journal of Cell Science, vol.125, issue.2, pp.265-275, 2012.
DOI : 10.1242/jcs.091280

M. Hein, N. Hubner, I. Poser, J. Cox, N. Nagaraj et al., A Human Interactome in Three Quantitative Dimensions Organized by Stoichiometries and Abundances, Cell, vol.163, issue.3, pp.712-723, 2015.
DOI : 10.1016/j.cell.2015.09.053

R. Hinterleitner, T. Gruber, C. Pfeifhofer-obermair, C. Lutz-nicoladoni, A. Tzankov et al., Adoptive Transfer of siRNA Cblb-Silenced CD8+ T Lymphocytes Augments Tumor Vaccine Efficacy in a B16 Melanoma Model, PLoS ONE, vol.7, issue.9, p.44295, 2012.
DOI : 10.1371/journal.pone.0044295.t002

V. Horejsi, W. Zhang, and B. Schraven, Transmembrane adaptor proteins: organizers of immunoreceptor signalling, Nature Reviews Immunology, vol.168, issue.8, pp.603-616, 2004.
DOI : 10.1091/mbc.E03-08-0574

F. Huang and H. Gu, Negative regulation of lymphocyte development and function by the Cbl family of proteins, Immunological Reviews, vol.204, issue.1, pp.229-238, 2008.
DOI : 10.1111/j.1600-065X.2008.00655.x

J. Hukelmann, K. Anderson, L. Sinclair, K. Grzes, A. Murillo et al., The cytotoxic T cell proteome and its shaping by the kinase mTOR, Nature Immunology, vol.34, issue.1, pp.104-112, 2016.
DOI : 10.1093/nar/gkn923

S. Hunter, E. Burton, S. Wu, and S. Anderson, Fyn Associates with Cbl and Phosphorylates Tyrosine 731 in Cbl, A Binding Site for Phosphatidylinositol 3-Kinase, Journal of Biological Chemistry, vol.274, issue.4, pp.2097-2106, 1999.
DOI : 10.1074/jbc.274.4.2097

M. Junttila, S. Saarinen, T. Schmidt, J. Kast, and J. Westermarck, -tag?? purification for the isolation and identification of protein complexes from mammalian cells, PROTEOMICS, vol.68, issue.5, pp.1199-1203, 2005.
DOI : 10.1002/pmic.200400991

URL : https://hal.archives-ouvertes.fr/hal-00882629

F. Kontgen, G. Suss, C. Stewart, M. Steinmetz, and H. Bluethmann, gene in C57BL/6 mice, International Immunology, vol.5, issue.8, pp.957-964, 1993.
DOI : 10.1093/intimm/5.8.957

J. Krumsiek, K. Suhre, T. Illig, J. Adamski, and F. Theis, Gaussian graphical modeling reconstructs pathway reactions from high-throughput metabolomics data, BMC Systems Biology, vol.5, issue.1, p.21, 2011.
DOI : 10.1186/1752-0509-5-21

H. Lee and A. Tsygankov, Cbl-family proteins as regulators of cytoskeleton-dependent phenomena, Journal of Cellular Physiology, vol.276, issue.12, pp.2285-2293, 2013.
DOI : 10.1002/jcp.24412

Y. Liu, Y. Liu, N. Meller, L. Giampa, C. Elly et al., Protein kinase C activation inhibits tyrosine phosphorylation of Cbl and its recruitment of Src homology 2 domain-containing proteins, J Immunol, vol.162, pp.7095-7101, 1999.

J. Liu, S. Deyoung, J. Hwang, O. Leary, E. Saltiel et al., The Roles of Cbl-b and c-Cbl in Insulin-stimulated Glucose Transport, Journal of Biological Chemistry, vol.278, issue.38, pp.36754-36762, 2003.
DOI : 10.1074/jbc.M300664200

F. Lozano, M. Simarro, J. Calvo, J. Vila, O. Padilla et al., CD5 Signal Transduction: Positive or Negative Modulation of Antigen Receptor Signaling, Critical Reviews??? in Immunology, vol.20, issue.4, pp.347-358, 2000.
DOI : 10.1615/CritRevImmunol.v20.i4.30

B. Luis and N. Carpino, Insights into the suppressor of T-cell receptor (TCR) signaling-1 (Sts-1)-mediated regulation of TCR signaling through the use of novel substrate-trapping Sts-1 phosphatase variants, FEBS Journal, vol.62, issue.3, pp.696-707, 2014.
DOI : 10.1111/febs.12615

B. Malissen and P. Bongrand, Early T Cell Activation: Integrating Biochemical, Structural, and Biophysical Cues, Annual Review of Immunology, vol.33, issue.1, pp.539-561, 2015.
DOI : 10.1146/annurev-immunol-032414-112158

M. Mcgavin, K. Badour, L. Hardy, T. Kubiseski, J. Zhang et al., The Intersectin 2 Adaptor Links Wiskott Aldrich Syndrome Protein (WASp)-mediated Actin Polymerization to T Cell Antigen Receptor Endocytosis, The Journal of Experimental Medicine, vol.57, issue.12, pp.1777-1787, 2001.
DOI : 10.1083/jcb.148.5.1047

M. Naramura, I. Jang, H. Kole, F. Huang, D. Haines et al., c-Cbl and Cbl-b regulate T cell responsiveness by promoting ligand-induced TCR down-modulation, Nature Immunology, vol.3, issue.12, pp.1192-1199, 2002.
DOI : 10.1038/ni855

O. Panasenko, The role of the E3 ligase Not4 in cotranslational quality control, Frontiers in Genetics, vol.23, issue.e1001342, p.141, 2014.
DOI : 10.1091/mbc.E12-02-0112

M. Paolino, C. Thien, T. Gruber, R. Hinterleitner, G. Baier et al., Essential Role of E3 Ubiquitin Ligase Activity in Cbl-b-Regulated T Cell Functions, The Journal of Immunology, vol.186, issue.4, pp.2138-2147, 2011.
DOI : 10.4049/jimmunol.1003390

D. Pe-'er, Bayesian network analysis of signaling networks: a primer, Sci STKE, p.4, 2005.

C. Pena-rossi, L. Zuckerman, J. Strong, J. Kwan, W. Ferris et al., Negative regulation of CD4 lineage development and responses by CD5, J Immunol, vol.163, pp.6494-6501, 1999.

S. Pettitt, Q. Liang, X. Rairdan, J. Moran, H. Prosser et al., Agouti C57BL/6N embryonic stem cells for mouse genetic resources, Nature Methods, vol.60, issue.7, pp.493-495, 2009.
DOI : 10.1002/1526-968X(200011/12)28:3/4<106::AID-GENE30>3.0.CO;2-T

K. Reginald, K. Chaoui, R. Roncagalli, M. Beau, G. Menoita et al., Revisiting the Timing of Action of the PAG Adaptor Using Quantitative Proteomics Analysis of Primary T Cells, The Journal of Immunology, vol.195, issue.11, pp.5472-5481, 2015.
DOI : 10.4049/jimmunol.1501300

N. Roa, D. Ordonez-rueda, J. Chavez-rios, C. Raman, E. Garcia-zepeda et al., The carboxy-terminal region of CD5 is required for c-CBL mediated TCR signaling downmodulation in thymocytes, Biochemical and Biophysical Research Communications, vol.432, issue.1, pp.52-59, 2013.
DOI : 10.1016/j.bbrc.2013.01.086

C. Rodriguez, F. Buchholz, J. Galloway, R. Sequerra, J. Kasper et al., High-efficiency deleter mice show that FLPe is an alternative to Cre-loxP, Nat Genet, vol.25, pp.139-140, 2000.

R. Roncagalli, S. Hauri, F. Fiore, Y. Liang, Z. Chen 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, Nature Immunology, vol.269, issue.4, pp.384-392, 2014.
DOI : 10.2202/1544-6115.1027

C. Rorsman, M. Tsioumpekou, C. Heldin, and J. Lennartsson, The Ubiquitin Ligases c-Cbl and Cbl-b Negatively Regulate Platelet-derived Growth Factor (PDGF) BB-induced Chemotaxis by Affecting PDGF Receptor ?? (PDGFR??) Internalization and Signaling, Journal of Biological Chemistry, vol.291, issue.22, pp.11608-11618, 2016.
DOI : 10.1074/jbc.M115.705814

S. Luis, B. Sondgeroth, B. Nassar, N. Carpino, and N. , Sts-2 Is a Phosphatase That Negatively Regulates Zeta-associated Protein (ZAP)-70 and T Cell Receptor Signaling Pathways, Journal of Biological Chemistry, vol.286, issue.18, pp.15943-15954, 2011.
DOI : 10.1074/jbc.M110.177634

S. Satpathy, S. Wagner, P. Beli, R. Gupta, T. Kristiansen et al., Systems-wide analysis of BCR signalosomes and downstream phosphorylation and ubiquitylation, Molecular Systems Biology, vol.11, issue.6, p.810, 2015.
DOI : 10.15252/msb.20145880

M. Schmidt and I. Dikic, The Cbl interactome and its functions, Nature Reviews Molecular Cell Biology, vol.4, issue.12, pp.907-918, 2005.
DOI : 10.1038/nrm1762

M. Shamim, S. Nanjappa, A. Singh, E. Plisch, S. Leblanc et al., Cbl-b Regulates Antigen-Induced TCR Down-Regulation and IFN-?? Production by Effector CD8 T Cells without Affecting Functional Avidity, The Journal of Immunology, vol.179, issue.11, pp.7233-7243, 2007.
DOI : 10.4049/jimmunol.179.11.7233

P. Soriano, The PDGF alpha receptor is required for neural crest cell development and for normal patterning of the somites, Development, vol.124, pp.2691-2700, 1997.

H. Tanno, T. Yamaguchi, E. Goto, S. Ishido, and M. Komada, The Ankrd 13 family of UIM-bearing proteins regulates EGF receptor endocytosis from the plasma membrane, Molecular Biology of the Cell, vol.23, issue.7, pp.1343-1353, 2012.
DOI : 10.1091/mbc.E11-09-0817

A. Tarakhovsky, S. Kanner, J. Hombach, J. Ledbetter, W. Muller et al., A role for CD5 in TCR-mediated signal transduction and thymocyte selection, Science, vol.269, issue.5223, pp.535-537, 1995.
DOI : 10.1126/science.7542801

C. Teh, S. Daley, A. Enders, and C. Goodnow, T-cell regulation by casitas B-lineage lymphoma (Cblb) is a critical failsafe against autoimmune disease due to autoimmune regulator (Aire) deficiency, Proceedings of the National Academy of Sciences, vol.107, issue.33, pp.14709-14714, 2010.
DOI : 10.1073/pnas.1009209107

S. Vardhana, K. Choudhuri, R. Varma, and M. Dustin, Essential Role of Ubiquitin and TSG101 Protein in Formation and Function of the Central Supramolecular Activation Cluster, Immunity, vol.32, issue.4, pp.531-540, 2010.
DOI : 10.1016/j.immuni.2010.04.005

H. Wang, J. Holst, S. Woo, C. Guy, M. Bettini et al., Tonic ubiquitylation controls T-cell receptor:CD3 complex expression during T-cell development, The EMBO Journal, vol.80, issue.7, pp.1285-1298, 2010.
DOI : 10.1038/emboj.2010.10

URL : https://hal.archives-ouvertes.fr/hal-00553208

S. Xu, J. Huo, J. Tan, and K. Lam, Cbp Deficiency Alters Csk Localization in Lipid Rafts but Does Not Affect T-Cell Development, Molecular and Cellular Biology, vol.25, issue.19, pp.8486-8495, 2005.
DOI : 10.1128/MCB.25.19.8486-8495.2005

M. Yang, T. Chen, X. Li, Z. Yu, S. Tang et al., K33-linked polyubiquitination of Zap70 by Nrdp1 controls CD8+ T cell activation, Nature Immunology, vol.1, issue.12, pp.1253-1262, 2015.
DOI : 10.1038/ni.3258

Y. Zheng, C. Zhang, D. Croucher, M. Soliman, N. St-denis et al., Temporal regulation of EGF signalling networks by the scaffold protein Shc1, Nature, vol.4, issue.7457, pp.166-171, 2013.
DOI : 10.1038/nature12308

Z. Zhou, H. Gao, C. Zhou, Y. Chang, J. Hong et al., Differential ubiquitin binding of the UBA domains from human c-Cbl and Cbl-b: NMR structural and biochemical insights, Protein Science, vol.4, issue.10, pp.1805-1814, 2008.
DOI : 10.1110/ps.036384.108

P. Zhou, D. Shaffer, A. Arias, D. Nakazaki, Y. Pos et al., In vivo discovery of immunotherapy targets in the tumour microenvironment, Nature, vol.165, issue.7486, pp.52-57, 2014.
DOI : 10.1073/pnas.0832254100